Alport syndrome clinical guidelines. Hereditary nephritis (Alport syndrome) in children. Symptoms of Alport syndrome in children

Alport syndrome is a hereditary disorder that manifests itself in the early onset of kidney failure, hearing loss and visual impairment.

This syndrome is a hereditary form of inflammation of the kidneys - jade. It's connected with a mutation in a protein gene, called collagen.

The disorder is rarely seen. More often it occurs at the stronger sex.

Women can pass on the gene for the disorder to their children, even if they don't have symptoms.

To risk factors relate:

Severe kidney disease in male relatives;
family history of the disorder;
Hearing loss up to 30.

Clinical picture

Symptoms may already be present in the first year of life crumbs, but most often manifested at 3–5 years old.

In most children, the predisposing condition is past infection. Due to the lack of manifestation, the disease may be detected by chance according to the results of urine tests.

This type of nephritis in children can take the form of hematuric glomerulonephritis or pyelonephritis.

initial stage deviations are inherent no complaints. During normal kidney function, only changes in urine: erythrocytes, leukocytes, protein appear.

Development of the disorder associated with nephrotic syndrome and high blood pressure. Patients have the following symptoms:

weakness,
pain in the head,
visual impairment, hearing loss,
pressure drop,
skin pallor,
lethargy.

The difference between Alport's syndrome in children and other forms of nephritis is damage to the auditory nerve.

The difficulty is that it can be identified only after audiometry, which is carried out after 7 years. Only 20% of children have visual impairments, and thrombocytopenia is observed only in some cases.

Deafness is more often manifested in boys - they also have an increase in pressure and a progressive decrease in kidney function much faster.

By the age of 18 the development of the disease causes a complete set manifestations of renal failure:

skin pallor,
dry mouth
nausea,
trembling of the hands and fingers,
a decrease in the volume of excreted urine or its complete absence,
sometimes there is an ache in the muscles and joints.

Without timely replacement therapy or transplant of a diseased kidney human lifespan will not exceed 40 years.

Syndrome forms:

autosomal recessive

With this type of inheritance, the mutated gene appears only when one recessive gene is received from the father, and the second from the mother.

Risk the appearance of an unhealthy baby is 25%.

Sick boys and girls are born equally often.

Parents of sick babies may appear healthy but are carriers of an unhealthy gene.

autosomal dominant

Dominant inheritance, based on the X chromosome, is that the action of the dominant unhealthy gene is manifested regardless of gender.

More hard the disorder resolves in boys.

One of the child's parents is certainly not healthy. Among the children of a man, sons are healthy, and daughters are sick. Women pass on the mutated gene to 50% of their sons and daughters.

How to diagnose a disease?

Syndrome is suspected based on pedigree by the presence of the disorder in other relatives. For the diagnosis of the disease, it is necessary to the presence of three out of five indicators:

Hematuria or death from kidney failure in the family;
Hematuria or proteinuria in relatives;
Detection of changes in organ biopsy;
hearing loss;
congenital visual impairment.

Diagnostics violations are carried out in the following ways:

Collection and study of anamnesis;
Physical method;
Laboratory tests;
ultrasound study,
Computed or magnetic tomography;
Scintigraphy;
Biopsy.

The distinguishing diagnosis of the disorder is distinction between nephritis and nephropathy.

Is it possible to treat Alport syndrome?

There is no specific treatment. Great importance is attached pressure control and dietary protein restriction when kidney function starts to decline.

As XHH progresses, patients are given hemodialysis treatment.

People with the syndrome are shown to have a kidney transplant, although in some situations, Goodpasture's syndrome may occur after a transplant.

Therefore, the selection of donors must be carried out very carefully.

In the absence of specific treatment, the main goal is to slow the development of kidney failure.

children prohibited physical activity, a balanced diet is prescribed.

Special attention is paid to treatment of infectious foci.

The use of hormonal agents and cytostatics does not cause significant improvement. The main treatment remains organ transplant.

Poor prognosis of the course of the disease, which is characterized by the rapid development of terminal renal failure, is likely in the presence of such indicators:

Male gender;
High protein content in urine;
Early appearance of kidney disorders in relatives;
Hearing loss.

Upon detection hematuria without proteinuria and hearing loss the prognosis for the course of the disorder is favorable, failure does not occur.

The course of the syndrome is progressive and not progressive, the prognosis is positive in women without hearing changes.

Each patient has his own degree of development of the process in the kidneys.

In 50% of boys, the last stage of kidney failure occurs by the age of 30, and sometimes even by 20 years. In others, the process develops more slowly, but eventually causes a violation of the kidneys.

Girls the disorder progresses more slowly and does not affect life expectancy, even with persistent microhematuria.

Dialysis and organ transplant favor a more positive prognosis.

Video: What you need to know about hereditary diseases

Useful information about hereditary diseases, which will help to avoid the development of many diseases in the unborn child. If you take into account these tips, then the likelihood of having a child with hereditary abnormalities will decrease significantly.

Alport syndrome is a hereditary disease in which the decline in kidney function is constantly progressing. In addition, along with the syndrome, deafness and blindness develop.

Such syndromes are caused by a gene located in the long arm of the X chromosome in the 21-22 q zone. Alporta gets sick if the structure of type IV collagen is disturbed - the protein that forms the basis of connective tissues is responsible for making them strong and elastic. So, with the disease, there is a defect in the collagen of the vascular walls of the kidneys, Corti's organs in the ears, and lens capsules in the eyes.

Classification and symptoms

Hereditary nephritis has three variants:

In the first variant along with the syndrome, nephrotic syndromes, hematuria appear, deafness develops and the eyes are affected. In this case, nephritis progresses to chronic renal failure. Inherited by dominant type. Basement membranes are thinned and split, their structure is broken.

Second option develops along with nephritis and hematuric manifestations, but hearing is not reduced. Nephritis also progresses and reaches CRF. The basement membranes of the glomerular capillaries are also thinned.

Third type benign familial hematuria. The course of the disease is benign, CRF does not occur.

Alport syndrome in children can manifest itself with quite different symptoms. Most often, the manifestations of the disease become noticeable by 5-10 years. The first symptomatology of Alport's syndrome (isolated urinary syndrome) appears in the first three years of a child's life. Most often, the disease is discovered by chance during a preventive examination of the baby. During this period, the baby feels absolutely normal, and only the urinary syndrome does not recede.

The main symptom of the disease is hematuria. It can manifest itself in different degrees, and is observed ALWAYS! It can intensify during and after infectious lesions that affect the respiratory tract, as well as during physical exertion. Especially excessive ones. Often, parents can sound the alarm after routine vaccinations - because they also provoke an exacerbation of hematuria.

The inconstancy of proteinuria is also noted, especially when the disease is just beginning to develop. And the more obvious the symptoms of the underlying disease become, the more pronounced proteinuria. Sometimes leukocytes are found in the urine sediment, but there are no bacteria in the urine.

Over time, the partial functions of the kidneys are disturbed, the patient's condition becomes worse - intoxications are noted (patients turn pale, quickly get tired, complain of headaches), weakness appears in the muscles, signs of hypertension increase, hearing and vision are impaired.

At first, hearing loss is determined only during a special test - audiography.

Hearing loss is possible at any age. Most often, deafness occurs in 6-10-year-old children, and in some cases - faster than the urinary syndrome.

Approximately 20% of patients have reduced vision. Most often this happens due to damage to the lens. Very often, family members in which Alport syndrome is prone to suffer from myopia.

Many children with hereditary nephritis, especially if kidney failure is formed against its background. Lagging behind in physical development. Often, against the background of kidney failure, arterial hypertension develops.

Most patients with Alport syndrome have dysembryogenesis stigmas (more than seven). They are manifested by small external deviations, but practically do not affect the functions of the body. Such stigmas include epicanths (folds at the inner corner of the eye), deformed auricles, high palate, fused fingers, or an increased number of them.

So, hereditary nephritis proceeds in stages - first in a latent form, when the clinical symptoms are hidden, and the urinary syndrome is minimally manifested. Further, decompensatory processes begin, in which the functioning of the kidneys decreases and manifest clinical symptoms appear.

Diagnostics

Hereditary nephritis in children is easy to assume if the pedigree is known and the same symptoms were present in other family members. To diagnose a disease, at least three of the possible five criteria must be identified:

Hematuria in relatives, or death due to chronic renal failure
Hematuria and/or proteinuria in relatives
Changes of a specific nature, which are determined by a biopsy
Deafness
Abnormal vision (most often congenital)

When it comes to hereditary diseases, besides congenital, diagnosis should always be comprehensive. Particular attention should be paid to the compilation of the pedigree of the baby.

Clinical and genetic research methods are mandatory for Alport syndrome and must necessarily include the collection of an anamnesis of the disease, as well as a general examination of the patient.

In the compensatory stages of the disease, it can only be detected based on hereditary burden, hypotension, multiple stigmas and altered urinary syndrome.

Differential diagnosis is also essential. First of all, one should not confuse the hematuric form of glomerulonephritis with Alport, otherwise the therapy chosen as a result of an incorrect diagnosis will be completely ineffective. In addition, dysmetabolic nephropathy and other kidney diseases should be distinguished from Alport's syndrome.

Therapeutic measures

First of all, the patient should be protected from excessive physical stress, children with pathology are exempted from physical education lessons. Frequent and long walks in the fresh air are recommended. The dietary regimen should be complete, contain proteins, fats and carbohydrates. But nutrition is developed and selected taking into account all the functions of the kidneys.

With Alport syndrome, it is necessary to identify and sanitize all possible infectious foci in time.

Among the drugs most often used are ATP, cocarboxylase, pyridoxine (up to 50 mg / day), carnitine chloride.

Hematuria is treated using herbal medicine. For these purposes, dioecious nettle, chokeberry juice and yarrow are used. For example, it is possible to prepare tinctures. Mix dioica nettle with shepherd's purse and horsetail. All herbs need 10 g each. Mix the collection well, measure out two small spoons, pour two glasses of boiling water and leave to infuse for at least 8 hours. After that, we pass through gauze, add glasses of water and take 100 ml every other day.

Patients with chronic renal failure are shown hemodialysis, and with chronic renal failure, an organ transplant is almost always needed.

There is no specific therapy that would get rid of hereditary nephritis. Therapeutic measures have one goal - to prevent and slow down the decline in kidney function.

A prerequisite is to limit the contact of sick children with infectious patients, as well as to reduce the risk of developing acute respiratory infections in such children. With hereditary nephritis, children are not vaccinated, although epidemiological vaccination is possible.

Hormones and immunosuppressive drugs in the syndrome do not have the desired effects. However, if cyclosporine A and ACE inhibitors are used for too long, some positive effect can be achieved - to reduce the level of proteinuria, to somewhat slow down the progression of the disease.

But the use of drugs that improve metabolic processes is shown. In this regard, pyridoxine, cocarboxylase, ATP, vitamins A and E can be effective. The above drugs improve the general condition, reduce tubular dysfunction. They are taken in special courses three times a year.

However, kidney transplantation remains the most effective treatment for hereditary nephritis today. As a rule, the disease does not recur in transplanted organs. And only occasionally (in about 5% of cases) does nephritis develop. However, it is associated with antigens to the glomerular basement membrane.

Prenatal diagnosis and genetic engineering treatment are extremely important and promising. In recent years, many experiments have been carried out on animals, which have shown and proved the effectiveness of the transfer of normal genes that are responsible for the synthesis of type IV collagen a-chains into the kidney tissue. After that, in almost all cases, normal collagen structures are synthesized.

Forecasting

It is difficult to predict anything with Alport syndrome. The only thing that can be said is that such forecasting is not always favorable. Especially if the patient is male, he has developed early kidney failure, there is severe proteinuria, thickened glomerular basement membranes, neuritis of the auditory nerves. Much more favorable prognosis for benign familial hematuria.

First described Zamelson and Dickinson (F. Samelsohn, W. H. Dickinson) in 1873 -1875. Later, Guthrie (L. G. Guthrie, 1902) suggested the existence of a special form of hereditary nephropathy, clinically similar to chronic nephritis. Alport followed the fate of several families, examined some of them who had previously been observed in Guthrie, and found deafness in many. Since 1961 the hereditary nephrite which is combined with deafness is called Alport's syndrome [Williamson (D. A. Williamson)].

Etiology.

Alport syndrome is inherited in a sex-linked dominant manner. The mutant gene is associated with the X chromosome, which may determine a more severe course of the disease in males. Whether the combination of clinical syndromes of damage to the kidneys and organs of hearing is associated with a mutation of one or more genes has not yet been established.

Pathological anatomy.

The morphological picture of the kidneys in Alport syndrome depends on the age of the patient and the period of the disease. The initial stage of the disease, according to puncture biopsy, is characterized by the absence of histological changes in the kidney tissue. An early pathoanatomical sign is the detection of erythrocytes in the lumen of the renal tubules. Subsequently, infiltration of the interstitial tissue appears (as a result of metabolic disorders and accumulation of metabolites in the kidney tissue, in particular lipoid substances), glomerular damage in the form of endothelial proliferation, thickening of the basement membrane, interstitial fibrosis, vascular hyalinosis.

In some cases, so-called foam cells are found. During this period, Alport's syndrome. it is difficult to differentiate with acquired glomerulo- or pyelonephritis.

Histological examination of the inner ear reveals atrophy of the ganglion cells of the auditory apparatus.

clinical picture.

The disease develops slowly. The earliest sign of Alport's syndrome is hematuria, often there is a slight proteinuria, less often leukocyturia. Hematuria can be in the first year of a child's life, but most often it is detected at the age of 7-10 years by chance, during dispensary examinations, against the background of intercurrent diseases. In boys, Alport's syndrome progresses steadily until the development of renal failure. Children lag behind in development. In girls and women, hereditary nephritis has a relatively more benign course, manifested by persistent hematuria, only during pregnancy, renal failure is possible.

Alport syndrome is characterized by the absence of an acute onset of the disease and extrarenal manifestations of nephritis. Edema and hypertension syndromes as a result of renal failure (but not the activity of the process) appear only in adolescence and in adults. Studies of protein, lipid metabolism, non-specific indicators of the immune process do not reveal pronounced changes. The functions of the adrenal cortex do not change. Immunological changes are characterized by an increase in the content of immunoglobulins G in the blood not only in the proband, but also in his relatives. Deafness develops later in the disease or may be absent altogether. It is observed in 16% of patients. Less commonly, eye lesions (cataract, spherophakia with secondary myopia, retinitis pigmentosa), malformations of the urinary tract are detected. Radiologically, most patients have unilateral or bilateral pyelectasis.

Alport syndrome (SA) is an inherited type IV collagen disorder characterized by a combination of progressive hematuric nephritis with ultrastructural changes and sensorineural hearing loss. Visual disturbances are also common in this syndrome. Microhematuria, detected in the early stages of life, is a constant characteristic sign of the disease.

Recurrent episodes of gross hematuria occur in about 60% of patients under 16 years of age, but are rare in adults. Over time, it joins and the disease progresses with age, depending on the gender of the patient and the type of inheritance of the disease. is a late sign.

Bilateral sensorineural hearing loss, affecting high and medium frequency hearing, is progressive in children, but may come to light later. There are reports of several types of visual disturbances, also progressive with age. Anterior lenticonus is a cone-shaped protrusion of the anterior part of the lens. Yellowish spots appear on the retina of the eye, which are asymptomatic. Both types of lesions are specific and occur in about a third of patients. There are also reports of recurrent corneal erosions in SA patients.

Morphology

Under light microscopy, kidney tissue obtained in the early stages of AS appears normal. Focal and segmental thickening of the capillary walls of the glomeruli, better detected by silver staining, become visible with the progression of the disease. They are associated with nonspecific tubular lesions and interstitial fibrosis. Standard immunofluorescence is usually negative. However, faint and/or focal grade G and M deposits and/or complement fraction C3 may be detected. The main damage is detected by the ultrastructural method. They are characterized by thickening (up to 800-1200 nm) with splitting and fragmentation of the lamina densa into several fibers forming a basket-like network. Changes can be fragmentary (heterogeneous), alternating with areas of normal or reduced thickness. In general, the most prominent feature in children is the uneven alternation of very thick and very thin areas of the GBM. Diffuse thinning of the GBM is found in about 20% of patients with SA.

At the genetic level, AS is a heterogeneous disease: mutations in COL4A5 on the X chromosome are associated with X-linked AS, while mutations in COL4A3 or COL4A4 on chromosome 2 are associated with autosomal forms of the disease.

X-linked Alport syndrome.

clinical symptoms.

The X-linked variant is the most common form of SA, characterized by a more severe course of the disease in male patients than in female patients, and the absence of transmission through the male line. Availability hematuria is a necessary criterion for diagnosis. gradually increases with age and can subsequently lead to the development of nephrotic syndrome. In all male patients, the disease progresses to end-stage kidney disease. There are two types of AS - juvenile, in which ESRD develops around the age of 20 in men with maternal transmission, and adult, characterized by a more variable course and development of ESRD around the age of 40. In heterozygous females, hematuria is found only in adulthood. It is absent in less than 10% of women (carriers). The risk of developing ESRD in women under the age of 40 is about 10-12% (against 90% in men), but increases after age 60. Most heterozygotes never develop ESRD. Bilateral sensorineural hearing loss progresses in most male patients and in some females. Changes in the organ of vision, anterior lenticonus and/or perimacular spots are observed in 1/3 of patients. In families with AS, women may have diffuse esophageal leiomyomatosis, which also includes lesions of the tracheobronchial tree and genital tract of women and sometimes congenital cataracts.

Molecular genetics made it possible to establish the features of mutations in the COL4A5 gene. They cause differences in clinical manifestations, course and prognosis.

Autosomal recessive Alport syndrome

Alport syndrome is inherited in an autosomal recessive manner in about 15% of affected families in Europe. This type of inheritance is more common in countries with higher levels of consanguineous marriages. Clinical symptoms and ultrastructural changes are identical to those observed in X-linked AS. However, some signs clearly indicate recessive inheritance: consanguineous marriages, severe disease in female patients, absence of severe disease in parents, microhematuria in the father. The disease, as a rule, progresses early to ESRD, almost always there are hearing impairments, not always - damage to the organ of vision.

Among heterozygotes, persistent or intermittent microhematuria is noted.

Autosomal dominant Alport syndrome

Autosomal dominant inheritance, characterized by transmission through the male line, is rare. The clinical phenotype is the same for men and women. The course is milder than in the X-linked form, with late and inconsistent progression to the development of ESRD and hearing loss. Heterozygous mutations in the COL4A3 or COL4A4 genes have been identified in some families.

Diagnosis and treatment of Alport's syndrome. Diagnosis of AS and determination of the type of inheritance are important for therapeutic management, prognosis, and genetic counseling of patients and their families. The issue is easily resolved if hematuria is combined with deafness or eye damage and if the hereditary history is sufficiently informative to establish the type of inheritance. Each incidentally discovered hematuria requires examination of other family members. The early onset of hematuria and the identification of sensorineural hearing loss, lenticonus, or maculopathy on careful examination may suggest SA, but the mode of inheritance remains uncertain. Determination of mutations in the COL4A5, COL4A3, or COL4A4 genes is critical for diagnosing the disease, but molecular analysis is a costly and time-consuming procedure due to the large size of the type IV collagen gene and the wide variety of mutations.

It is important to differentiate Alport syndrome from thin basement membrane disease (TBM) early. This is best done on the basis of family history: the presence in the family of adult men over 35 years of age with hematuria and intact renal function with a high probability allows us to make a diagnosis of TBM.

In the absence of hearing loss, diagnosis is quite difficult: if you do a kidney biopsy too early (before 6 years), you can not see the changes characteristic of Alport syndrome that will develop later, and electron microscopy is not available everywhere. In this regard, it is promising to introduce an immunohistochemical method for determining the expression of various type IV collagen chains in the renal tissue or in the skin.

Sporadic hematuria with proteinuria, detected in the absence of extrarenal manifestations, is the reason for a renal biopsy to exclude other hematuric glomerulopathies (IgA nephropathy, etc.). Progression to end-stage kidney disease is inevitable in X-linked SA in men and in all patients with autosomal recessive SA. To date, there is no specific treatment. The main treatment is blockade of the renin-angiotensin system to reduce and possibly slow down the progression. Kidney transplantation leads to satisfactory results, however, about 2.5% of all patients with SA develop anti-GBM due to the formation of a "different" donor GBM, which leads to graft rejection.

Alport syndrome is a hereditary disease that is directly characterized by a consistent decrease in kidney function, coupled with pathology of hearing and even vision. At the moment, in our country, this kind of illness among children (mainly) is approximately 17: 100,000.

Main reasons

According to experts, Alport syndrome occurs due to abnormalities in the gene, which is located on the long arm of the X chromosome in the so-called zone 21-22q. In addition, a violation of the integral structure of the so-called type 4 collagen is also the cause of this disease. Collagen is understood in science as such a protein, which is a direct component of the connective tissue, ensuring its elasticity and continuity.

Symptoms

Alport syndrome usually first manifests itself in children between the ages of five and ten and manifests itself in the form of hematuria (blood in the urine). Most often, this diagnosis is detected randomly, that is, during the next examination by a specialist. In addition, Alport's syndrome also manifests itself in the form of the so-called stigmas of dysembryogenesis. These are relatively small deviations that do not play a special role in the functioning of the main body systems. Doctors note epicanthus (a small fold at the inner corner of the eye), a high palate, a slight deformation of both auricles, and other signs. Consistent is also a sure sign of this disease, and hearing loss is much more often diagnosed in boys. All of the above symptoms are most often found in adolescence, while the common chronic one makes itself felt only during adulthood.

Diagnosis

Alport syndrome in children is usually diagnosed based on the presence of this kind of ailment in other family members. For example, to confirm the disease, it is enough to meet three of the five criteria listed below:

hearing loss;
cases of death from chronic renal failure of close relatives;
confirmation of hematuria in family members;
vision pathology;
the presence of specific changes during a kidney biopsy.

In the absence of specific therapy, doctors must first slow the development of kidney failure. With such a diagnosis as Alport's disease, physical activity is strictly forbidden for children, they are prescribed. Important attention is paid to the sanitation of the so-called infectious foci. The use of cytostatics and various kinds of hormonal drugs in the treatment improves the condition. However, it is most often prescribed as a primary method of treatment. It should be noted that when hematuria is detected without significant hearing impairment, the overall prognosis for the course of the disease is somewhat more favorable. In a situation of this kind, renal failure is diagnosed extremely rarely.

Alport syndrome (familial glomerulonephritis) is a rare genetic disorder characterized by glomerulonephritis, progressive renal failure, sensorineural hearing loss, and eye involvement.

The disease was first described by British physician Arthur Alport in 1927.

Alport syndrome is very rare, but in the US it is responsible for 3% of ESRD in children and 0.2% in adults, and is also considered the most common type of familial nephritis.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.
Autosomal recessive (ARAS): 15%.
Autosomal dominant (ADAS): 1%.

The most common X-linked form of Alport syndrome results in end-stage renal disease in men. Hematuria usually occurs in boys with Alport syndrome in the first years of life. Proteinuria is usually absent in childhood, but the condition often develops in men with XLAS and in both sexes with ARAS. Hearing loss and eye involvement are never detected at birth but occur in late childhood or adolescence, shortly before kidney failure develops.

Causes and mechanism of development of Alport syndrome

Alport syndrome is caused by mutations in the COL4A4, COL4A3, COL4A5 genes responsible for collagen biosynthesis. Mutations in these genes disrupt the normal synthesis of type IV collagen, which is a very important structural component of basement membranes in the kidneys, inner ear and eyes.

Basement membranes are thin film structures that support tissues and separate them from each other. In violation of the synthesis of type IV collagen, the glomerular basement membranes in the kidneys are not able to normally filter toxic products from the blood, passing proteins (proteinuria) and red blood cells (hematuria) into the urine. Abnormalities in type IV collagen synthesis lead to kidney failure and kidney failure, which is the main cause of death in Alport syndrome.

Clinic

Hematuria is the most common and early manifestation of Alport's syndrome. Microscopic hematuria is observed in 95% of women and in almost all men. In boys, hematuria is usually detected in the first years of life. If a boy does not have hematuria in the first 10 years of life, then American experts recommend that he is unlikely to have Alport syndrome.

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare.

Hypertension is more commonly present in male patients with XLAS and in patients of both sexes with ARAS. The frequency and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss (hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing impairment is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually presents in the first years of life or early adolescence. At an early stage of the disease, hearing impairment is determined only by audiometry.

As it progresses, the hearing loss extends to low frequencies, including human speech. After the onset of hearing loss, kidney involvement should be expected. American scientists claim that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%.

Anterior lenticonus (protrusion of the central part of the lens of the eye forward) occurs in 25% of patients with XLAS. Lenticonus is not present at birth, but over the years it leads to a progressive deterioration of vision, which forces patients to change their glasses frequently. The condition is not accompanied by eye pain, redness, or impaired color vision.

Retinopathy is the most common manifestation of Alport's syndrome on the part of the organ of vision, affecting 85% of men with an X-linked form of the disease. The onset of retinopathy usually precedes kidney failure.

Posterior polymorphic corneal dystrophy is a rare condition in Alport syndrome. Most have no complaints. Mutation L1649R in the collagen gene COL4A5 can also cause retinal thinning, which is associated with X-linked Alport syndrome.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition seen in some families with Alport syndrome. Symptoms appear in late childhood and include swallowing disorders (dysphagia), vomiting, epigastric and retrosternal pain, frequent bronchitis, shortness of breath, cough. Leiomyomatosis is confirmed by computed tomography or MRI.

Autosomal recessive form of Alport syndrome

ARAS accounts for only 10-15% of cases. This form occurs in children whose parents are carriers of one of the affected genes, the combination of which causes the disease in the child. The parents themselves are asymptomatic or have minor manifestations, and the children are severely ill - their symptoms resemble XLAS.

Autosomal dominant form of Alport syndrome

ADAS is the rarest form of the syndrome, affecting generation after generation, with males and females equally severely affected. Renal manifestations and deafness resemble XLAS, but renal failure may occur later in life. Clinical manifestations of ADAS are complemented by a tendency to bleeding, macrothrombocytopenia, Epstein's syndrome, and the presence of neutrophilic inclusions in the blood.

Diagnosis of Alport's syndrome

Laboratory tests. Urinalysis: Patients with Alport's syndrome most often have blood in the urine (hematuria) as well as a high protein content (proteinuria). Blood tests show kidney failure.
tissue biopsy. Kidney tissue obtained from a biopsy is examined using electron microscopy for the presence of ultrastructural abnormalities. A skin biopsy is less invasive and US experts recommend doing it first.
Genetic analysis. In the diagnosis of Alport syndrome, if doubts remain after a kidney biopsy, genetic analysis is used to obtain a definitive answer. Mutations of type IV collagen synthesis genes are determined.
Audiometry. All children with a family history suggestive of Alport syndrome should have high-frequency audiometry to confirm sensorineural hearing loss. Periodic monitoring is recommended.
Eye examination. Examination by an ophthalmologist is very important for early detection and monitoring of anterior lenticonus and other abnormalities.
Ultrasound of the kidneys. In advanced stages of Alport's syndrome, ultrasound of the kidneys helps to identify structural abnormalities.

British experts, based on new data (2011) on genetic mutations in patients with X-linked Alport syndrome, recommend testing for COL4A5 gene mutation if the patient meets at least two diagnostic criteria according to Gregory, and analysis of COL4A3 and COL4A4 if the COL4A5 mutation is not autosomal inheritance is found or suspected.

Alport Syndrome Treatment

Some researchers suggest that ciclosporin may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports say that patients' response to ciclosporin is highly variable, and sometimes the drug can precipitate interstitial fibrosis.

In renal failure, standard therapy includes erythropoietin to treat chronic anemia, drugs to control osteodystrophy, correction of acidosis, and antihypertensive therapy to control blood pressure. Hemodialysis and peritoneal dialysis are used. Kidney transplantation is not contraindicated for patients with Alport's syndrome: transplantation experience in the USA has shown good results.

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

Konstantin Mokanov

Alport's syndrome is a genetic disorder of the kidneys, accompanied by a decrease in visual acuity and hearing. According to statistics, about 17 cases are diagnosed per 100 thousand people. It is most common in men, but women also get sick. Usually the first symptoms appear at the age of 3-8 years, but it can also occur without characteristic signs.

In official medicine, there are several forms and stages of Alport Syndrome. Each of them has a number of characteristic symptoms, as well as the severity of the course of the disease. The main forms of the syndrome include:

Hereditary nephritis in children is characterized by the presence of only renal symptoms. At the same time, the decrease in hearing and vision in patients is not observed.
When examining kidney tissue, an isolated thinning of the basement membranes occurs.
The disease is accompanied not only by pathologies of the kidneys, but also manifests itself in the form of hearing and vision impairment.

Alport syndrome is classified according to the severity and rate of progression of symptoms. There are 3 types:

The disease progresses extremely quickly, and goes into renal failure. In this case, the symptoms are pronounced.
The disease progresses quite quickly, but does not affect hearing and vision.
The course of the disease is benign. There are no characteristic symptoms, as well as progression.

Reasons for development

The only cause of Alport syndrome in humans is a genetic mutation. 3 genes are damaged, which are located on the 2nd chromosome. It is in them that information is stored about the chains of collagens that affect the functioning of the kidneys.

The damaged gene is most often inherited by a child from his parents on the X chromosome. In this regard, the pathology can be transmitted to children of any sex from the mother, and from the father - only to the girl. The probability of being born with kidney damage is higher if there are people in the family with hereditary diseases of the urinary system.

For every fifth birth of a child with Alport syndrome, there is an accidental gene mutation. At the same time, parents and close relatives have no genetic disorders and perfectly healthy kidneys.

Symptoms

The clinical symptoms of Alport's syndrome are pronounced. The initial stage is accompanied by hearing loss and the presence of blood in the urine.

However, if the disease progresses, then the symptoms are more pronounced. Intoxication of the body occurs, and anemia develops. This is due to a sharp decrease in hemoglobin levels. As a result, additional symptoms appear:

drops in blood pressure;
frequent headache;
rapid shallow breathing;
noise in ears;
fast fatiguability.

Another characteristic feature is a violation of the biological rhythm. Sleepiness during the day and insomnia at night most often occurs in young children and the elderly. General symptoms depend on the age and health status of the patient.

The chronic form of Alport's syndrome is accompanied by symptoms such as:

frequent urination that does not bring relief;
malaise;
the presence of blood in the urine;
convulsions;
general weakness;
nausea accompanying vomiting;
lack of appetite;
chest pain;
bruising and itchy skin.

In rare cases, a patient with chronic Alport syndrome falls into unconsciousness or suffers from confusion. However, in children, such symptoms practically do not occur.

Treatment Methods

Alport syndrome is currently considered an incurable disease. But there are studies based on the results of which (with the progression of renal failure), it is effective to use ACE inhibitors - drugs used to treat and prevent heart disease. According to the second studies, it is effective to use ATII receptor antagonists. Both types of drugs reduce intraglomerular pressure, which can significantly reduce proteinuria. In addition, inhibition of angiotensin-II can reduce vascular sclerosis.

At the very beginning, there is a study whose task is to prove the effect of cyclosporine on the normalization of renal function. But this drug in some cases leads to an acceleration of interstitial fibrosis.

Modern laboratories are studying the treatment of the disease with the help of gene therapy, but it is premature to talk about any results.

Shock, complex treatment is applicable only if there is a clear threat to life. At the initial stage, the disease is not treated.

If a child has kidney symptoms, it is necessary to adhere to a special regimen and follow the doctor's recommendations, which consist of the following measures:

The child should be exempt from serious physical exertion - it is not recommended to attend physical education classes and go to sports sections.
Frequent outdoor walks are recommended.
When blood in the urine or other symptoms appear, herbal medicine can be used. It is effective to drink chokeberry juice, as well as a decoction or infusion of yarrow and nettle.
You should eat right. Smoked, salty, fatty, spicy and spicy dishes should be absent from the diet. It is best to avoid products that contain artificial colors. Alcohol with such a disease is completely prohibited, but with the development of anemia, the patient can drink a small amount of dry red wine.
To improve metabolism, you need to drink a complex of vitamins: E, A and B6. It is better to take courses for two weeks.
To increase metabolism, it is also recommended to inject Cocarboxylase.

Genetically determined non-immune glomerulopathy, occurring with hematuria, a progressive decrease in renal function, is Alport's syndrome or hereditary nephritis. It is manifested by a complex of pathologies: the presence of nephritis with hematuria, hearing loss and vision pathology. In this article, we will tell you about the main causes and symptoms of the syndrome, as well as how it is treated in a child.

Causes of Alport syndrome in children

According to epidemiological studies conducted in 13 regions of Russia, this disease occurs with a frequency of 17 per 100,000 children [Ignatova M. S, 1999].

Etiology of Alport syndrome

The genetic basis of the disease is a mutation in the a-5 gene of the type IV collagen chain. This type is universal for the basement membranes of the kidney, cochlear apparatus, lens capsule, retina and cornea of the eye, which has been proven in studies using monoclonal antibodies against this collagen fraction. Recently, the possibility of using DNA probes for prenatal diagnosis of the disease has been pointed out [Tsalikova F.D. et al., 1995].

Most patients with Alport's syndrome, families have people with kidney disease, hearing loss and vision pathology, family marriages between people with one or more ancestors are important, tk. in the marriage of related individuals, the probability of obtaining the same genes from both parents increases [Fokeeva V. V. et al., 1988]. Autosomal dominant and autosomal recessive and dominant, X-linked transmission pathways have been established.

In babies, three variants of Alport syndrome are more often distinguished:

the syndrome itself
hereditary nephritis without hearing loss,
familial benign hematuria.

The pathogenesis of Alport's syndrome

It is based on a combined defect in the collagen structure of the basal membrane of the glomeruli of the kidneys, structures of the ear and eye. The gene for the classic syndrome is located at the locus 21-22 q of the long arm of the X chromosome. In most cases, it is inherited in a dominant type linked to the X chromosome. In this regard, in men, Alport syndrome is more severe, since in women the function of the mutant gene is compensated by a healthy allele of the second, intact chromosome.

When examining a kidney biopsy according to electron microscopy, the following symptoms are observed: ultrastructural changes in the glomerular basement membrane: thinning, disruption of the structure and splitting of the glomerular basement membranes with a change in its thickness and uneven contours. In the early stages of the disease, the defect determines the thinning and fragility of the glomerular basement membranes.

Thinning of the glomerular membranes is more benign and is more common in girls. A more constant electron microscopic sign in this disease is the splitting of the basement membrane, and the severity of its destruction correlates with the severity of the process.

What are the symptoms of Alport syndrome in children?

The first symptoms of the disease in the form of an isolated urinary syndrome are more often detected in children of the first three years of life. In most cases, the disease is discovered incidentally. Urinary syndrome is detected during a preventive examination of a child, before admission to a children's institution or during SARS. In the case of the appearance of pathology in the urine during ARVI, in the syndrome, in contrast to acquired glomerulonephritis, there is no latent period.

How does Alport syndrome manifest itself in the initial stage?

In the initial stage, the child's well-being suffers little, the symptoms are not clearly expressed, treatment is carried out according to the doctor's recommendations. A characteristic feature is the persistence and persistence of the urinary syndrome. One of the main signs is hematuria of varying severity, observed in 100% of cases. An increase in the degree of hematuria is noted during or after respiratory tract infections, exercise, or after preventive vaccinations. Proteinuria in most cases does not exceed 1 g / day, at the beginning of the disease it can be unstable, as the process progresses, proteinuria increases. Periodically, leukocyturia with a predominance of lymphocytes may be present in the urinary sediment, which is associated with the development of interstitial changes.

In the future, there is a violation of the partial functions of the kidneys, a deterioration in the general condition of the patient: intoxication, muscle weakness, arterial hypotension, often hearing loss (especially in boys), sometimes visual impairment. Intoxication is manifested by pallor, fatigue, headaches.

Hearing loss is a symptom of Alport's syndrome.

In the initial stage of the disease, hearing loss in most cases is detected only with the help of audiography. Hearing loss can occur at various times during childhood, but hearing loss is most often diagnosed between the ages of 6 and 10 years. It begins with high frequencies, reaching a significant degree with air and bone conduction, moving from sound-conducting to sound-perceiving hearing loss. Hearing loss may be one of the first symptoms of the disease and may precede urinary syndrome.

Decreased vision - a symptom of Alport's syndrome

In 20% of cases, patients have changes in the organs of vision. Anomalies from the side of the lens are most often detected: spherofokia, anterior, posterior or mixed lenticonus, various cataracts. In families with this disease, there is a significant incidence of myopia. A number of researchers constantly note bilateral perimacular changes in these families in the form of bright whitish or yellowish granulations in the area of the corpus luteum. They consider this symptom to be a permanent symptom that has a high diagnostic value in this disease. K. S. Chugh et al. (1993) in an ophthalmological examination revealed a decrease in visual acuity in patients in 66.7% of cases, anterior lenticonus in 37.8%, retinal spots in 22.2%, cataracts in 20%, keratoconus in 6.7 %.

Features of Alport syndrome in children

In some children, especially in the formation of renal failure, a significant lag in physical development is noted. As renal failure progresses, arterial hypertension develops. In a child, its symptoms are more often detected in adolescence and in older age groups. When diagnosed, treatment is carried out immediately.

It is characteristic that patients with Alport syndrome have a variety of (more than 5 - 7) stigmas of connective tissue dysembryogenesis [Fokeeva VV, 1989]. Among the connective tissue stigmas in patients, the most common hypertelorism of the eyes, high palate, malocclusion, abnormal shape of the auricles, curvature of the little finger on the hands, "sandal gap" on the feet. The disease is characterized by the following symptoms: uniformity of dysembryogenesis stigmas within the family, as well as a high frequency of their spread among relatives of the probands through which the disease is transmitted.

In the early stages of the disease, an isolated decrease in the partial functions of the kidneys is detected: the transport of amino acids, electrolytes, concentration function, acidogenesis, in the future, changes relate to the functional state of both the proximal and distal nephron and are in the nature of combined partial disorders. The decrease in glomerular filtration occurs later, more often in adolescence. As it progresses, anemia develops.

Thus, the staging of the course of the disease is characteristic: first, a latent stage or latent clinical symptoms, manifested by minimal changes in the urinary syndrome, then a gradual decompensation of the process occurs with a decrease in renal functions with overt clinical symptoms (intoxication, asthenia, developmental delay, anemization). Clinical symptoms usually appear regardless of the layering of the inflammatory reaction.

The syndrome can manifest itself at different age periods, which depends on the action of the gene, which is in a repressed state until a certain time.

How is Alport syndrome diagnosed in children?

The following criteria are proposed:

The presence in each family of at least two patients with nephropathy,
Hematuria as a leading symptom of nephropathy in the proband,
The presence of hearing loss in at least one of the family members,
Development of CRF in one relative or more.

When diagnosing a variety of hereditary and congenital diseases, a large place belongs to an integrated approach to examination and, above all, paying attention to the data obtained when compiling a child's pedigree. The diagnosis of Alport's syndrome is considered eligible in cases where 3 out of 4 typical signs are found in a patient: the presence of hematuria and chronic renal failure in the family, the presence of neurosensory hearing loss in the patient, pathology of vision, the detection of signs of splitting of the glomerular basement membrane with a change in its thickness and uneven contours in the electron microscopic characteristic of the biopsy specimen with a change in its thickness and uneven contours [Ignatova M. S, 1996].

Clinical and genetic methods for the study of Alport's syndrome

Before treatment begins, the patient is examined, which should include clinical and genetic methods of research, a directed study of the history of the disease, a general examination of the patient, taking into account diagnostically significant criteria.

In the stage of compensation, pathology can be caught only by focusing on such syndromes as the presence of hereditary burden, hypotension, multiple stigmas of dysembryogenesis, and changes in the urinary syndrome.
In the stage of decompensation, estrarenal symptoms may appear, such as severe intoxication, asthenization, lag in physical development, anemization, which manifest and intensify with a gradual decrease in renal functions. In most patients, with a decrease in renal functions, there is a decrease in the function of acido- and aminogenesis, in 50% of patients a significant decrease in the secretory function of the kidneys, limiting the limits of fluctuations in the optical density of urine, a violation of the filtration rhythm, and then a decrease in glomerular filtration.
The stage of chronic renal failure is diagnosed in the presence of patients for 3-6 months. and more elevated levels of urea in the blood serum (more than 0.35 g / l), a decrease in glomerular filtration rate up to 25% of the norm.

Differential diagnosis of Alport syndrome

It has to be carried out with the hematuric form of acquired glomerulonephritis. Acquired glomerulonephritis often has an acute onset, a period of 2–3 weeks after infection, extrarenal signs, including hypertension from the first days (with Alport's syndrome, on the contrary, hypotension), a decrease in glomerular filtration at the onset of the disease, no violation of partial tubular functions, then as in hereditary they are present. Acquired glomerulonephritis occurs with more pronounced hematuria and proteinuria, with increased ESR. Typical changes in the glomerular basement membrane characteristic of the syndrome are of diagnostic value. Treatment must be started promptly.

Differential diagnosis from dysmetabolic nephropathy is carried out with chronic renal failure, heterogeneous kidney diseases are clinically detected in the family, and there may be a spectrum of nephropathy from pyelonephritis to urolithiasis. Often there are complaints of pain in the abdomen and periodically during urination, in the urine sediment - oxalates.

If a disease is suspected, the patient must be referred to a specialized nephrology department to clarify the diagnosis.

How to treat Alport syndrome in children?

The treatment regimen provides for restriction from heavy physical exertion, stay in the fresh air. During the period when the treatment is carried out, a complete diet is indicated, with a sufficient content of complete proteins, fats and carbohydrates, taking into account kidney function. Of great importance is the identification and sanitation of chronic foci of infection. Of the drugs, ATP, cocarboxylase, pyridoxine (up to 50 mg / day), vitamin B5, carnitine chloride are used. Courses are held 2-3 times a year. With hematuria, herbal medicine is prescribed - nettle nettle, chokeberry juice, yarrow.

In foreign and domestic literature, there are reports of treatment with prednisolone and the use of cytostatics. However, it is difficult to judge the effect.

Alport Syndrome Treatment

In chronic renal failure, hemodialysis and kidney transplantation are used.

MS Ignatova (1999) believes that the main method in the development of chronic renal failure is the timely implementation of kidney transplantation, which is possible without prior extracorporeal dialysis. The problem of using genetic engineering methods is topical.

There is a need for continuity in the constant monitoring of patients and the transfer of children by a pediatrician directly to a nephrologist. Dispensary observation is carried out throughout the life of the patient.

Now you know the main symptoms and treatments for Alport syndrome in children. Health to your baby!

Alport's syndrome is a hereditary disease that manifests itself in the early development of renal failure, a decrease in hearing and visual acuity.

The disease is caused by genetic mutations affecting the connective tissue type 4 collagen, which is an integral part of many important structures in the body, including the kidneys, inner ear and eyes.

Alport syndrome is much more difficult to tolerate by males. The fact is that the disease is most often transmitted through a mutated X chromosome. Since girls have two X chromosomes, the healthy one works as a spare and facilitates the course of the disease.

In Alport's syndrome, due to the inability of the kidneys to eliminate toxins, poisoning of the body occurs. Therefore, in females, this pathology can cause infertility. And if pregnancy does occur, the toxins can kill both the baby and the mother. Often, Alport's syndrome manifests itself during pregnancy, even if it did not make itself felt before.

Symptoms of the disease

As Wikipedia says about such an ailment as Alport syndrome, this hereditary disease is characterized by hematuria (blood in the urine), leukocyturia (detection of leukocytes in the urine test), proteinuria (the presence of protein in the urine), deafness or hearing loss, sometimes cataracts and the development of kidney failure in adolescence. age. Sometimes kidney damage can occur only after 40-50 years.

The main symptom of the disease is the presence of blood in the urine, which indicates kidney disease. Sometimes it can only be detected microscopically, and in some cases the urine may turn pink, brown or red, especially against the background of connected infections, flu or viruses in the body. With age, in addition to hematuria, protein appears in the urine and the patient has arterial hypertension.

Although Wikipedia describes Alport syndrome as a disease that manifests as cataracts, this is not always the case. Sometimes, abnormal retinal pigmentation can also occur, significantly impairing vision. In addition, the cornea with such a hereditary disease is prone to the development of erosion. Therefore, they need to protect their eyes from getting foreign objects in them.

Alport syndrome also characterizes hearing loss, which usually manifests itself in adolescence. This problem is solved with the help of a hearing aid.

Alport syndrome: treatment and prevention

Alport's syndrome, the treatment of which is mainly symptomatic, involves the mandatory rehabilitation of chronic foci of infections. Patients with this disease are contraindicated to be vaccinated in a quiet time from epidemics. There are also contraindications to taking glucocorticoid drugs. Dialysis is used for kidney failure, and its development after the age of 20 is an indication for kidney transplantation.

Regarding the prevention of pathology, one should beware of urinary tract infections, which accelerate the development of renal failure. Women with Alport syndrome who decide to have a baby should first consult with a geneticist who will help identify the carrier of the mutant gene. Although statistics show that about 20% of families with Alport syndrome do not have relatives suffering from kidney failure. This fact proves that a mutated gene can occur spontaneously.

To protect your descendants from such a hereditary disease as Alport syndrome, it is necessary to avoid consanguineous marriages. And if the carrier of the abnormal gene is identified, in order to eradicate the pathology in the future, you can use donor genetic material and resort to the procedure of insemination or artificial insemination. In each individual case, an individual consultation of specialists is necessary.

SyndromeAlporta(SA, synonym: hereditary nephritis) is a non-immune genetically determined glomerulopathy caused by a mutation of the genes encoding type 4 collagen of basement membranes, manifested by hematuria and / or proteinuria, a progressive decrease in renal function, often combined with pathology of hearing and vision (NG).

The disease was first described by British physician Arthur Alport in 1927.

According to epidemiological data in Russia, the frequency of SA among the child population was 17:100,000 of the population.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.

Autosomal recessive (ARAS): 15%.

Autosomal dominant (ADAS): 1%. The most common X-linked form of Alport syndrome results in end-stage renal disease in men. Hematuria usually occurs in boys with Alport syndrome in the first years of life. Proteinuria is usually absent in childhood, but the condition often develops in men with XLAS and in both sexes with ARAS. Hearing loss and eye involvement are never detected at birth but occur in late childhood or adolescence, shortly before kidney failure develops. The most common type of Alport syndrome is caused by mutations in genes located on the long arm of the X chromosome that are responsible for collagen biosynthesis. Mutations in these genes disrupt the normal synthesis of type IV collagen, which is a very important structural component of basement membranes in the kidneys, inner ear and eyes. In violation of the synthesis of type IV collagen, the glomerular basement membranes in the kidneys are not able to normally filter toxic products from the blood, passing proteins (proteinuria) and red blood cells (hematuria) into the urine. Abnormalities in type IV collagen synthesis lead to kidney failure and kidney failure, which is the main cause of death in Alport syndrome. Clinic:

Hematuria- This is the most frequent and early manifestation of Alport's syndrome. Microscopic hematuria is observed in 95% of women and in almost all men. In boys, hematuria is usually detected in the first years of life. If a boy does not have hematuria in the first 10 years of life, then experts recommend that he is unlikely to have Alport syndrome. Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare. Hypertension is more commonly present in male patients with an X-linked inheritance pattern and in patients of both sexes with an autosomal recessive pattern. The frequency and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss(hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing impairment is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually presents in the first years of life or early adolescence. At an early stage of the disease, hearing impairment is determined only by audiometry. As it progresses, the hearing loss extends to low frequencies, including human speech. After the onset of hearing loss, kidney involvement should be expected. Scientists say that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%. Anterior lenticonus(protrusion of the central portion of the lens of the eye forward) is observed in 25% of patients with X-linked inheritance. Lenticonus is not present at birth, but over the years it leads to a progressive deterioration of vision, which forces patients to change their glasses frequently. The condition is not accompanied by eye pain, redness, or impaired color vision.

retinopathy- this is the most common manifestation of Alport's syndrome on the part of the organ of vision, it affects 85% of men with an X-linked form of the disease. The onset of retinopathy usually precedes kidney failure.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition that occurs in some families with Alport syndrome. Symptoms appear in late childhood and include swallowing disorders (dysphagia), vomiting, epigastric and retrosternal pain, frequent bronchitis, shortness of breath, cough.

On the autosomal recessive form accounts for only 10-15% of cases. This form occurs in children whose parents are carriers of one of the affected genes, the combination of which causes the disease in the child. The parents themselves are asymptomatic or have minor manifestations, and the children are seriously ill - their symptoms resemble those of X-linked inheritance.

Autosomal dominant form of Alport syndrome- this is the rarest form of the syndrome, which affects one generation after another, with men and women equally severely ill. Renal manifestations and deafness resemble the X-linked form, but renal failure may occur later in life. Clinical manifestations of the autosomal dominant form are complemented by a tendency to bleeding, macrothrombocytopenia, Epstein's syndrome, and the presence of neutrophilic inclusions in the blood. Diagnosis of Alport's syndrome

Laboratory tests. Urinalysis: Patients with Alport's syndrome most often have blood in the urine (hematuria) as well as a high protein content (proteinuria). Blood tests show kidney failure (an increase in the number of white blood cells, an increase in the erythrocyte sedimentation rate (ESR) - a sign of infection, an inflammatory process; a decrease in the number of red blood cells and hemoglobin (anemia); a decrease in the number of platelets (usually small).

tissue biopsy. Kidney tissue obtained from a biopsy is examined using electron microscopy for the presence of ultrastructural abnormalities. A skin biopsy is less invasive and experts recommend doing it first.

Genetic analysis. In the diagnosis of Alport syndrome, if doubts remain after a kidney biopsy, genetic analysis is used to obtain a definitive answer. Mutations of type IV collagen synthesis genes are determined.

Audiometry. All children with a family history suggestive of Alport syndrome should have high-frequency audiometry to confirm sensorineural hearing loss. Periodic monitoring is recommended.

Eye examination. Examination by an ophthalmologist is very important for early detection and monitoring of anterior lenticonus and other abnormalities.

Ultrasound of the kidneys. In advanced stages of Alport's syndrome, ultrasound of the kidneys helps to identify structural abnormalities.

Alport Syndrome Treatment

Alport's syndrome is currently incurable. Studies have shown that ACE inhibitors can reduce proteinuria and slow the progression of kidney failure. Thus, the use of ACE inhibitors is reasonable in patients with proteinuria, regardless of the presence of hypertension. The same applies to ATII receptor antagonists. Both classes of drugs help reduce proteinuria by lowering intraglomerular pressure. Moreover, inhibition of angiotensin-II, the growth factor responsible for glomerular sclerosis, could theoretically slow down sclerosis. Some researchers suggest that ciclosporin may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports say that patients' response to ciclosporin is highly variable, and sometimes the drug can precipitate interstitial fibrosis.

Kidney transplantation is not contraindicated for patients with Alport's syndrome: transplantation experience in the USA has shown good results. Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

Secondary prevention.

In families with an X-linked form of SA, with known mutations, prenatal diagnosis is possible, which is extremely important if the fetus is male

The importance of testing all family members using DNA probes to identify carriers of the mutant gene is emphasized, which is of great importance when conducting medical genetic counseling for families with this disease. However, up to 20% of families do not have relatives suffering from kidney disease, which suggests a high frequency of spontaneous mutations of the abnormal gene. Most patients with hereditary nephritis in families have people with kidney disease, hearing loss and vision pathology; related marriages between people with one or more ancestors are important, since in the marriage of related individuals, the probability of receiving the same genes from both parents increases. Autosomal dominant and autosomal recessive and dominant, X-linked transmission pathways have been established.

In children, three variants of hereditary nephritis are more often distinguished: Alport syndrome, hereditary nephritis without hearing loss, and familial benign hematuria.

Alport syndrome — hereditary nephritis with hearing loss. It is based on a combined defect in the collagen structure of the basal membrane of the glomeruli of the kidneys, structures of the ear and eye. The gene for classic Alport syndrome is located at the locus 21-22 q of the long arm of the X chromosome. In most cases, it is inherited in a dominant type linked to the X chromosome. In this regard, in men, Alport syndrome is more severe, since in women the function of the mutant gene is compensated by a healthy allele of the second, intact chromosome.

The genetic basis for the development of hereditary nephritis are mutations in the genes of type IV collagen alpha chains. Six a-chains of type IV collagen G are known: the genes for a5- and a6-chains (Col4A5 and Col4A5) are located on the long arm of the X-chromosome in the zone 21-22q; genes of а3- and а4-chains (Сol4A3 and Сol4A4) — on the 2nd chromosome; genes a1- and a2-chains (Col4A1 and Col4A2) - on the 13th chromosome.

In most cases (80-85%), an X-linked type of inheritance of the disease is detected, associated with damage to the Col4A5 gene as a result of deletion, point mutations, or splicing disorders. Currently, more than 200 mutations of the Col4A5 gene have been found, which are responsible for impaired synthesis of a5-chains of type IV collagen. With this type of inheritance, the disease manifests itself in children of both sexes, but in boys it is more severe.

Mutations in the loci of the Col4A3 and Col4A4 genes responsible for the synthesis of a3- and a4-type IV collagen chains are inherited autosomal. According to studies, an autosomal dominant type of inheritance is observed in 16% of cases of hereditary nephritis, autosomal recessive - in 6% of patients. About 10 mutation variants of the Col4A3 and Col4A4 genes are known.

The result of mutations is a violation of the assembly processes of type IV collagen, leading to a violation of its structure. Collagen type IV is one of the main components of the glomerular basement membrane, the cochlear apparatus and the lens of the eye, the pathology of which will be detected in the clinic of hereditary nephritis.

Type IV collagen, which is part of the glomerular basement membrane, consists mainly of two a1-chains (IV) and one a2-chain (IV), and also contains a3, a4, a5-chains. Most often, in X-linked inheritance, the mutation of the Col4A5 gene is accompanied by the absence of a3-, a4-, a5- and a6 chains in the structure of type IV collagen, and the number of o1- and a2-chains in the glomerular basement membrane increases. The mechanism of this phenomenon is unclear, it is assumed that the cause is post-transcriptional changes in mRNA.

The absence of a3-, a4- and a5-chains in the structure of type IV collagen of the glomerular basement membranes leads to their thinning and fragility in the early stages of Alport's syndrome, which is clinically manifested more often by hematuria (less often hematuria with proteinuria or only proteinuria), hearing loss and lenticonus. Further progression of the disease leads to thickening and impaired permeability of the basement membranes in the later stages of the disease, with the growth of type V and VI collagen in them, manifested in an increase in proteinuria and a decrease in renal function.

The nature of the mutation underlying hereditary nephritis largely determines its phenotypic manifestation. With deletion of the X chromosome with simultaneous mutation of the Col4A5 and Col4A6 genes responsible for the synthesis of a5- and a6-chains of type IV collagen, Alport's syndrome is combined with leiomyomatosis of the esophagus and genital organs. According to studies with a mutation in the Col4A5 gene associated with a deletion, there is a greater severity of the pathological process, a combination of renal damage with extrarenal manifestations and early development of chronic renal failure, compared with a point mutation of this gene.

Morphologically, electron microscopy reveals thinning and stratification of glomerular basement membranes (especially lamina densa) and the presence of electron-dense granules. Glomerulus involvement can be heterogeneous in the same patient, ranging from minimal focal mesangial involvement to glomerulosclerosis. Glomerulitis in Alport syndrome is always immuno-negative, which distinguishes it from glomerulonephritis. Characterized by the development of tubular atrophy, lymphohistiocytic infiltration, the presence of "foam cells" with lipid inclusions - lipophages. With the progression of the disease, thickening and pronounced destruction of the basement membranes of the glomeruli is revealed.

Certain shifts in the state of the immune system are revealed. In patients with hereditary nephritis, a decrease in the level of Ig A and a tendency to increase the concentration of IgM in the blood were noted, the level of IgG can be increased in the early stages of the disease and decrease in the later stages. It is possible that an increase in the concentration of IgM and G is a kind of compensatory reaction in response to IgA deficiency.

The functional activity of the T-lymphocyte system is reduced; there is a selective decrease in B-lymphocytes responsible for the synthesis of Ig A, the phagocytic link of immunity is disturbed, mainly due to disruption of the processes of chemotaxis and intracellular digestion in neutrophils

In the study of kidney biopsy in patients with Alport's syndrome, according to electron microscopy, ultrastructural changes in the glomerular basement membrane are observed: thinning, disruption of the structure and splitting of glomerular basement membranes with a change in its thickness and uneven contours. In the early stages of hereditary nephritis, the defect determines the thinning and fragility of the glomerular basement membranes.

Thinning of the glomerular membranes is more benign and is more common in girls. A more constant electron microscopic sign in hereditary nephritis is the splitting of the basement membrane, and the severity of its destruction correlates with the severity of the process.

Causes and mechanism of development of Alport syndrome

Clinic

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare.

Autosomal recessive form of Alport syndrome

Autosomal dominant form of Alport syndrome

Diagnosis of Alport's syndrome

Alport Syndrome Treatment

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

The true causes of the disease

The true causes of alport syndrome are still not fully understood by scientists. In our body there is a gene whose functional responsibility is the exchange of protein in the tissues of the kidneys. So the mutation of this gene is the most likely cause of the onset of the disease.

Now consider the provoking factors that can contribute to the onset of the disease. These include:

- severe infectious processes;
- vaccinations;
- strong physical activity.

As can be seen from numerous cases of medical practice, sometimes a common acute respiratory viral infection can contribute to the development of alport syndrome. It is in view of such high risks of morbidity that children who have a burdened heredity should undergo regular diagnostic examinations more often.

For the first time this disease was registered at the beginning of the last century. The doctor observed a family in which hematuria was observed for several generations. Later, a link was seen between hematuria and hearing loss, as well as eye damage. Later, when medicine improved, doctors more deeply investigated the genetic nature of this syndrome.

In most cases, its "owners" have relatives with kidney pathologies and other signs of this syndrome. Related marriages also play a role, as a result of which the child has an increased likelihood of receiving the same genes. Patients with Alport's syndrome show changes in the immune system.

Symptoms

Hereditary nephritis has a pronounced clinical symptomatology. If we talk about the initial stages of the pathological process, then it manifests itself as follows:

- the appearance of blood in the urine;
- deterioration of visual function;
- hearing impairment, up to the development of deafness.

Clinical symptoms will increase as the disease progresses. Over time, signs of intoxication appear, and anemia develops. The general condition and age of the patient affect the severity of the clinical picture.

Other characteristic symptoms of the disease are the following signs:

- severe headaches;
- muscle pain;
- even a little physical activity quickly tires the patient;
- dizziness;
- arterial hypertension, which is replaced by a sharp drop in pressure;
- dyspnea;
- shallow breathing;
- tinnitus that becomes permanent.

If we are talking about the chronic form of hereditary nephritis, the clinical picture here will be slightly different, namely:

- weakness and general malaise;
- frequent urge to urinate, blood impurities;
- urination does not bring relief;
- nausea and vomiting;
- loss of appetite and, consequently, weight loss;
- hemorrhage;
- skin itching;
- convulsions;
- pain in the chest;
- in severe cases, there is confusion and bouts of unconsciousness.

Infectious processes of the respiratory tract, active physical activity, preventive vaccinations - all this can provoke an increase in hematuria. As for the presence of protein in the urine, at first proteinuria is intermittent, and then gradually increases and becomes persistent.

Symptoms of intoxication also increase, hearing loss is especially observed in boys, children get tired quickly, they are worried about severe headaches. Children are significantly behind in physical development.

Kinds

Experts distinguish three types of Alport syndrome:

- pronounced symptoms and rapid progression of acute renal failure;
- the disease progresses rapidly, but there is no visual and hearing impairment;
- benign course of the disease, in which there are no clinical symptoms and progression. In this scenario, the prognosis is favorable. If a woman has an autosomal recessive type of inheritance, then a more severe course of the disease is observed.

Diagnostic examination

If there are suspicions of a hereditary factor in children, you should contact your pediatrician as soon as possible. To clarify the diagnosis, laboratory and instrumental research methods are used. As for laboratory diagnostics, it includes a general blood and urine test, as well as a biochemical study.

If we talk about instrumental diagnostics, then this includes the following:

- ultrasound examination of the kidneys and adrenal glands;
- kidney biopsy;
- kidney radiograph.

Sometimes additional genetic tests may be needed. Patients are assigned a consultation with a nephrologist and additionally - genetics.

The main criteria for a diagnostic examination are:

- the presence in the family of two people with nephropathy;
- hematuria is the dominant symptom;
- hearing loss in one of the family members;
- the occurrence of chronic renal failure in one of the relatives.

If we talk about differential analysis, then hereditary nephritis is compared with the acquired form of glomerulonephritis, in which hematuria is also observed. What is the difference? Glomerulonephritis has an acute onset and there is a direct relationship with the infection. If hereditary nephritis manifests itself in the form of arterial hypotension, then glomerulonephritis, on the contrary, is expressed in arterial hypertension.

Fighting methods

Treatment for alport syndrome involves a combination of medications and a special diet. It is worth noting that specific drugs that would eliminate this particular genetic disease still do not exist. The focus of drugs used in hereditary nephritis is associated with the normalization of kidney function. Diet food for children is prescribed by a doctor individually. As a rule, such prescriptions must be followed for the rest of your life. Outdoor walks are shown. In extreme cases, the specialist may decide to perform surgery. Usually, the operation is performed at the age of fifteen.

Proper nutrition

Immediately I want to note the foods that need to be excluded from the diet. These include:

- salty, fatty and smoked foods;
- spices and spicy food;
- alcoholic beverages, but sometimes doctors may prescribe red wine for medicinal purposes;
- products that contain artificial colors.

Food should be fortified and high-calorie, but without a high protein content. Physical activity is excluded. Sports, especially for children, can only take place if they are not prohibited by a doctor.

The food should be complete and contain enough proteins, fats and carbohydrates, while the functional abilities of the kidneys should be taken into account.

Renal failure is one of the most severe complications of Alport syndrome. According to statistics, boys from sixteen to twenty years old suffer from insufficiency. If there is no adequate treatment and the right way of life, then death occurs earlier than at the age of thirty.

In addition, it is important to avoid contact with infectious patients to reduce the risk of developing respiratory diseases. Preventive vaccinations are contraindicated in children with hereditary nephritis, and vaccination can be carried out only according to epidemiological indications.

There is no cure for Alport syndrome. This is a genetic disease that cannot be prevented. If the child has been diagnosed with an ailment, then you should follow the recommendations of the doctor and the right lifestyle.

If we talk about forecasts, then the following criteria are extremely unfavorable:

- male gender;
- the presence of chronic renal failure in family members;
- acoustic neuritis;
- the presence of protein in the urine.

Patients are prescribed drugs that affect the improvement of metabolism:

- vitamin A, E;
- pyridoxine;
- cocarboxylase.

Transplantation is the most effective treatment for Alport syndrome. The recurrence of the disease in the graft is not observed, and only in minor cases, the development of nephritis is possible.

So, alport syndrome is a serious illness that requires a timely and competent approach to treatment. There is no prevention of hereditary nephritis, but its course can be alleviated with strict adherence to all medical recommendations.

Hereditary nephritis (better known name - Alport syndrome) - pathology is quite rare. According to official data, in Russia, for every 100,000 newborn babies, there are 17 with such an anomaly of development. In Europe, 1% of all patients with chronic renal failure (CRF) are people with hereditary nephritis. And 2.3% of kidney transplants are performed on patients with this diagnosis.

Alport Syndrome?

Hereditary nephritis is a progressive kidney disease that often accompanies hearing loss and severe vision problems. In reference books, you can find the definition of Alport syndrome (SA) as a non-immune hereditary form of glomerulopathy, that is, damage to the glomerular apparatus of the kidneys.

Congenital disorder of renal function manifests itself in children as early as 3-5 years old, occurs due to mutations in one of the three genes that are responsible for the production of type IV collagen.

The fourth collagen variety forms the basis of the basement membranes of the renal glomeruli, the cochlear apparatus (part of the inner ear), and the lens capsule. Hence - and simultaneous violations of the kidneys, hearing and vision.

The International Classification of Diseases of the 10th revision (ICD-10), the main regulatory document that systematizes all existing health disorders, classifies a childhood disease as a class of congenital anomalies, deformities, and chromosomal disorders. Since a number of organs suffer from SA, the disease is included in the group of congenital malformations that affect several systems at once. And it is marked with the code Q87.8 - these are "other specified syndromes of congenital anomalies not classified elsewhere."

The reasons

The main and only reason why children are born with Alport syndrome is a genetic mutation. One of three genes is damaged - COL4A5, COL4A4, COL4A3. The COL4A5 gene is located on the X chromosome and encodes the a5-chain collagen chain. The "place of residence" of the COL4A3 and COL4A4 genes is the 2nd chromosome. They, respectively, store information about the chains of collagen a3- and a4-.

Most often, the damaged gene is passed on to the baby from the parents. When kidney disease passes along the X chromosome, the mother can become a transmitter of the anomaly to both her son and daughter. The father is only daughters. The likelihood that a baby will be born with kidney damage increases significantly if there are people in the family with diseases of the urinary system (primarily CRF).

But in 20% of cases, children with Alport syndrome are born in families where all relatives have perfectly healthy kidneys. Here we are talking about random, spontaneous genetic mutations.

Symptoms

Congenital hereditary nephritis develops with a lack of collagen, one of the main structural elements of connective tissue. As a result of collagen deficiency, the basement membranes of the renal glomeruli, the inner ear and the eye apparatus become thinner and split, and the organs themselves cease to fully cope with their function.

All symptoms of Alport's syndrome are divided into two groups - renal and extrarenal manifestations. Among the kidneys, two main signs are diagnosed: hematuria (traces of blood in the urine) and proteinuria (proteins in the urine). Often they are combined under the name "isolated urinary syndrome".

Isolated urinary syndrome in children can be noticed not immediately. Visible signals appear only at the 3-5th year of life, sometimes even at 7-10 years. But the smallest droplets of blood in the urine are always present, even if at first they are not visible - this is asymptomatic microhematuria. Therefore, hematuria is considered the main specific symptom of Alport syndrome.

In about half of the cases, the trigger for the appearance of blood in children's urine is an infection. Renal symptoms appear 1-2 days after SARS. Boys also develop proteinuria, but later, usually after 10 years of age. In girls, this symptom is either smoothed out or not at all.

Extrarenal symptoms of congenital nephritis appear later. It:

hearing loss (first the child ceases to distinguish between high sounds, then ordinary speech);
various eye disorders;
lag in physical development;
congenital anomalies (deformed ears, high palate, fused or additional fingers - no more than 7 signs);
rarely - leiomyomatosis (growth of smooth muscle fibers) of the esophagus, trachea, bronchi.

As the disease progresses, the classic signs of kidney failure appear: yellowish and dry skin, dry mouth, decreased urine output, etc. Increased pressure in the renal vessels - hypertension.

Classification

There are two classifications of Alport syndrome in children. The first is genetic, according to the type of inheritance of the anomaly.

In accordance with this classification, three types of congenital nephritis are distinguished:

X-linked dominant, or classic (about 80% of all patients with SA);
autosomal recessive (15% of children with a congenital anomaly);
autosomal dominant (the rarest type, about 5% of patients).

The second, main classification names three variants of kidney disease:

Nephritis accompanied by hematuria, hearing loss and vision problems (eye lesions). This is an X-dominant type of birth defect.
Nephritis with hematuria, but without involvement of the sense organs. Corresponds to the autosomal recessive form.
Benign familial hematuria.

The first two options are progressive renal disease, the inevitable outcome of which is chronic renal failure. With benign familial hematuria, CRF does not develop, and the quality and life expectancy do not suffer in any way.

Diagnostics

These signs include:

In the family there are cases of hematuria, in the family there were cases of death from chronic renal failure.
In the family, the child is diagnosed with hematuria and/or proteinuria.
Specific changes in the patient's basement membrane of the renal glomeruli (according to the results of a biopsy).
Congenital pathology of vision.
Hearing loss (detected by audiometry).

If Alport syndrome is suspected, a number of traditional diagnostic methods are used:

collection of anamnesis (information about the presence of the same symptoms and deaths from CRF in blood relatives);
physical methods (palpation, tapping);
laboratory tests (clinical urinalysis, etc.);
Ultrasound and kidney biopsy.

Experts also recommend a DNA test for family members of a young patient using DNA probes. This allows you to determine the carrier of the mutant gene. In addition, there is the possibility of using DNA probes for prenatal diagnosis of Alport's syndrome, even during the mother's pregnancy. This is especially important if the family is expecting a boy - SA is more severe in men.

Without fail, differential diagnosis is also required: to distinguish between congenital nephritis and nephropathy and acquired glomerulonephritis.

Treatment

At the initial stage of congenital nephritis, powerful complex therapy is not required.

When making a renal diagnosis, the following therapeutic measures for children are necessary:

lack of serious physical exertion (exemption from physical education lessons);
constant walks;
balanced diet;
herbal medicine for the appearance of blood in children's urine (nettle and yarrow infusion, chokeberry juice);
vitamins A and E, B6 (pyridoxine) to improve metabolism (courses of 2 weeks);
for the same purposes - injections of cocarboxylase.

When chronic renal failure passes into the most dangerous, terminal stage, permanent hemodialysis is required. In the most severe cases, a kidney transplant.

Forecast

The prognosis for Alport syndrome depends on two factors: the variant of the disease and the sex of the child. The classical, X-dominant form of Alport's syndrome progresses most rapidly in boys.

In this case, chronic renal failure is diagnosed in all patients under 60 years of age, and in 50% - up to 25 years. If there are men in the family with the same variant of nephritis, then the time of onset of the end stage of renal failure can be easily predicted, it will be the same. Women have no such dependence.

In the autosomal recessive type, kidney failure develops a little more slowly, but there is a risk that CRF will go into the terminal stage by the age of 30.

With an autosomal dominant form, the course and prognosis are the most favorable: the situation does not reach chronic renal failure. This form corresponds to benign familial hematuria. Specific therapy in this case is not carried out, the presence of blood in the urine does not threaten human life. All that is needed is constant medical monitoring of the patient's condition.

For the first time, this syndrome was described by the English physician Arthur Alport in 1927, who observed a whole family with total renal failure and simultaneous damage to the organs of vision and hearing in several generations.

Subsequently, conclusions were drawn about the genetic origin disease, which was ultimately proven in practice.

What it is?

Alport syndrome is a rare genetic disease associated with a violation of the structure of the fibrillar collagen protein, which is part of the kidneys, organs of vision and hearing of a person.

Due to the pathology, the patient develops renal failure, hearing deteriorates and visual acuity decreases. The disease is characterized by constant progress.

In medical practice, this syndrome has other names - hereditary nephritis or familial glomerulonephritis. The disease is hereditary and is associated with a pathology in one of the genes that is responsible for the structure of the collagen protein.

This compound serves as an integral part of the cochlear apparatus of the hearing organs, the lenses of the eyes and the glomerular apparatus of the kidneys. Due to this, the patient simultaneously develops a number of symptoms in the relevant organs: kidney failure, visual impairment and hearing loss.

According to the international classification according to ICD-10 has the code Q87.8(“Other Congenital Anomaly Syndromes”). That is, the disease refers to congenital pathologies with chromosomal abnormalities.

According to statistics, the number of people with this anomaly in the genes is about 0.017% throughout the planet, in the countries of North America the figure is several times higher. It is noticed that the mutated gene is more often activated in males.

Disease classification

Allocate 3 basic shapes diseases:

Dominant type of inheritance connected to the X chromosome. Thinning and splitting of the basal membrane in the kidneys, consisting of collagen, develops. Symptoms: hearing impairment, decreased vision, nephritis and hematuria. Constantly evolving.
Autosomal recessive type of inheritance. The clinical picture is similar to the previous type, but without hearing loss.
Autosomal dominant type of inheritance. It is called benign familial hematuria. Renal failure does not develop, the course of the disease is favorable.

The reasons

The main reason is the mutation of the genes responsible for the code of collagen chains.

This pathology is usually transmitted from parents to, in rare cases it occurs independently (20% of cases). Moreover, the mother passes on the X chromosome to the son and daughter, and the father can only pass on to the daughter.

Probability of developing the disease increases many times if close relatives had other chronic diseases of the genitourinary system. It is also noticed that the disease can be triggered by additional factors:

infectious diseases (viral, bacterial and fungal);
trauma;
taking medications;
vaccinations;
increased mental and physical stress;
stress and emotional overwork.

Symptoms of the disease

The first symptoms appear aged 3-6 years. Gene mutation leads to collagen deficiency, which in turn negatively affects the condition of the basement membrane in the kidneys, eye lenses and the structure of the inner ear. These organs are less functional.

First of all, the kidneys suffer - the ability to filter worsens, as a result of which proteins, toxins and red blood cells begin to enter the bloodstream. Develops progressive renal failure.

Simultaneously and with a delay, there is a decrease in visual acuity and hearing impairment. Symptoms tend to constantly grow and progress. The child may have additional symptoms:

blood in the urine;
elevated levels in the blood and urine;
anemia;
symptoms of intoxication (nausea, vomiting, weakness);
muscle pain;
jumps in blood pressure;
decreased physical activity;
headache;
insomnia;
increase in body temperature;
chills;
lagging behind in development from peers;
hearing loss (inability to distinguish between low and high tones);
lens anomalies.

In the future, without adequate treatment, the disease can become chronic, which is characterized by:

chronic fatigue;
constant malaise;
dry skin;
loss of appetite;
weight loss;
unpleasant taste in the mouth;
mental retardation and lethargy;
constant thirst and dry mouth;
pale skin color.

Diagnostic measures

First of all, the doctor studies the medical history of the parents, since the disease is transmitted from parents to children. in 4 cases out of 5. He pays attention to the following details in the child and parents:

the presence of hematuria;
kidney biopsy showed abnormalities in the basement membrane structure;
congenital problems with vision and hearing;
in the family there were cases of renal failure with a fatal outcome;
there is a constant decrease in hearing and vision in the child.

Enough the presence of 3 signs to almost certainly make a diagnosis. Further studies will be assigned in the form of:

kidney,
biopsies of collagen structures,
radiography,
urine and blood
consultations of a geneticist and a nephrologist.

How to treat pathology?

To date, the disease cannot be completely cured.

Complex of therapeutic measures helps to stop the progress of the disease. For this, medications and special nutrition are used, and there is no specific drug against this ailment.

Angiotensin-converting enzyme (ATP) inhibitors, as well as angiotensin blockers, are prescribed to slow down the development of renal failure. This reduces proteinuria (the level of protein in the urine) and normalizes kidney function.

Additional medications may include Erythropoietin in the presence of anemia and drugs to normalize blood pressure. Perhaps peritoneal dialysis and. In severe cases, the patient need a kidney transplant regardless of age.

As adjuvant therapy For children, it is important to follow a number of rules:

reduce physical activity (up to exemption from physical education lessons);
take vitamins A, B6 and E to normalize metabolic processes in the body;
take walks in the fresh air;
engage in herbal medicine to improve the functionality of the kidneys and cleanse the blood (use decoctions and infusions of yarrow, nettle and chokeberry juice).

It is worth considering separately food, which directly affects the kidneys and can both help and harm. The patient is forbidden to eat fatty, fried, salty, smoked and spicy. These types of foods overload the kidneys and can cause the disease to progress.

Also, you can not drink alcohol, with the exception of red wine in small quantities and only at the discretion of a doctor. Dangerous for health are any products with dyes in the composition (colored soda, jelly products with dye, etc.).

All food should be nutritious and contain as many vitamins as possible. At the same time, food should be well absorbed and not overload the digestive system, which affects the functioning of the kidneys. Lean meats (veal, lean beef), fish, seafood, poultry, as well as various vegetables and fruits are suitable for this.

Forecast

The prognosis depends on the form of the disease and the gender of the person. In the male line, the syndrome develops according to a similar scenario, so the father's history data can help predict the course of the disease in his son, such a dependence is not observed.

most dangerous is the X-dominant form, progressing rather quickly and posing a threat to life due to chronic renal failure. However, it is difficult to make an accurate prediction.

In contrast to the X-dominant form, the autosomal dominant type is less aggressive, and renal failure is less pronounced. It is possible to slow down the development of symptoms almost completely. The prognosis is favorable in most cases. The patient only needs constant monitoring of the condition of the kidneys and compliance. Medical therapy is usually not used.

Alport syndrome cannot be avoided as it is a genetic disease. There are no effective preventive measures. There are also no specific drugs against the disease. The main thing is to control the patient's condition.

When a disease is detected, it is necessary to undergo all examinations and follow the recommendations of doctors.

The only truly effective way kidney transplant, which is carried out with serious renal failure and a threat to the life of the patient.

Find out how a kidney transplant operation works from the video:

Hereditary nephritis in children is characterized by the presence of only renal symptoms. At the same time, the decrease in hearing and vision in patients is not observed.
When examining kidney tissue, an isolated thinning of the basement membranes occurs.
The disease is accompanied not only by pathologies of the kidneys, but also manifests itself in the form of hearing and vision impairment.

Alport syndrome is classified according to the severity and rate of progression of symptoms. There are 3 types:

The disease progresses extremely quickly, and goes into renal failure. In this case, the symptoms are pronounced.
The disease progresses quite quickly, but does not affect hearing and vision.
The course of the disease is benign. There are no characteristic symptoms, as well as progression.

Reasons for development

For every fifth birth of a child with Alport syndrome, there is an accidental gene mutation. At the same time, parents and close relatives have no genetic disorders and perfectly healthy kidneys.

Symptoms

The clinical symptoms of Alport's syndrome are pronounced. The initial stage is accompanied by hearing loss and the presence of blood in the urine.

drops in blood pressure;
frequent headache;
rapid shallow breathing;
noise in ears;
fast fatiguability.

The chronic form of Alport's syndrome is accompanied by symptoms such as:

frequent urination that does not bring relief;
malaise;
the presence of blood in the urine;
convulsions;
general weakness;
nausea accompanying vomiting;
lack of appetite;
chest pain;
bruising and itchy skin.

In rare cases, a patient with chronic Alport syndrome falls into unconsciousness or suffers from confusion. However, in children, such symptoms practically do not occur.

Treatment Methods

Modern laboratories are studying the treatment of the disease with the help of gene therapy, but it is premature to talk about any results.

Shock, complex treatment is applicable only if there is a clear threat to life. At the initial stage, the disease is not treated.

If a child has kidney symptoms, it is necessary to adhere to a special regimen and follow the doctor's recommendations, which consist of the following measures:

The child should be exempt from serious physical exertion - it is not recommended to attend physical education classes and go to sports sections.
Frequent outdoor walks are recommended.
When blood in the urine or other symptoms appear, herbal medicine can be used. It is effective to drink chokeberry juice, as well as a decoction or infusion of yarrow and nettle.
You should eat right. Smoked, salty, fatty, spicy and spicy dishes should be absent from the diet. It is best to avoid products that contain artificial colors. Alcohol with such a disease is completely prohibited, but with the development of anemia, the patient can drink a small amount of dry red wine.
To improve metabolism, you need to drink a complex of vitamins: E, A and B6. It is better to take courses for two weeks.
To increase metabolism, it is also recommended to inject Cocarboxylase.

Causes of Alport syndrome in children

According to epidemiological studies conducted in 13 regions of Russia, this disease occurs with a frequency of 17 per 100,000 children [Ignatova M. S, 1999].

Etiology of Alport syndrome

In babies, three variants of Alport syndrome are more often distinguished:

the syndrome itself
hereditary nephritis without hearing loss,
familial benign hematuria.

The pathogenesis of Alport's syndrome

What are the symptoms of Alport syndrome in children?

How does Alport syndrome manifest itself in the initial stage?

Hearing loss is a symptom of Alport's syndrome.

Decreased vision - a symptom of Alport's syndrome

Features of Alport syndrome in children

The syndrome can manifest itself at different age periods, which depends on the action of the gene, which is in a repressed state until a certain time.

How is Alport syndrome diagnosed in children?

The following criteria are proposed:

The presence in each family of at least two patients with nephropathy,
Hematuria as a leading symptom of nephropathy in the proband,
The presence of hearing loss in at least one of the family members,
Development of CRF in one relative or more.

Clinical and genetic methods for the study of Alport's syndrome

In the stage of compensation, pathology can be caught only by focusing on such syndromes as the presence of hereditary burden, hypotension, multiple stigmas of dysembryogenesis, and changes in the urinary syndrome.
In the stage of decompensation, estrarenal symptoms may appear, such as severe intoxication, asthenization, lag in physical development, anemization, which manifest and intensify with a gradual decrease in renal functions. In most patients, with a decrease in renal functions, there is a decrease in the function of acido- and aminogenesis, in 50% of patients a significant decrease in the secretory function of the kidneys, limiting the limits of fluctuations in the optical density of urine, a violation of the filtration rhythm, and then a decrease in glomerular filtration.
The stage of chronic renal failure is diagnosed in the presence of patients for 3-6 months. and more elevated levels of urea in the blood serum (more than 0.35 g / l), a decrease in glomerular filtration rate up to 25% of the norm.

Differential diagnosis of Alport syndrome

If a disease is suspected, the patient must be referred to a specialized nephrology department to clarify the diagnosis.

How to treat Alport syndrome in children?

In foreign and domestic literature, there are reports of treatment with prednisolone and the use of cytostatics. However, it is difficult to judge the effect.

Alport Syndrome Treatment

In chronic renal failure, hemodialysis and kidney transplantation are used.

Now you know the main symptoms and treatments for Alport syndrome in children. Health to your baby!

Alport syndrome (familial glomerulonephritis) is a rare genetic disorder characterized by glomerulonephritis, progressive renal failure, sensorineural hearing loss, and eye involvement.

The disease was first described by British physician Arthur Alport in 1927.

Alport syndrome is very rare, but in the US it is responsible for 3% of ESRD in children and 0.2% in adults, and is also considered the most common type of familial nephritis.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.
Autosomal recessive (ARAS): 15%.
Autosomal dominant (ADAS): 1%.

Causes and mechanism of development of Alport syndrome

Clinic

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare.

Autosomal recessive form of Alport syndrome

Autosomal dominant form of Alport syndrome

Diagnosis of Alport's syndrome

Alport Syndrome Treatment

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

Konstantin Mokanov