Alport syndrome is a genetically determined inflammatory disease of the kidneys, accompanied by damage to the auditory and visual analyzers. This is a fairly rare hereditary pathology that occurs in 1 out of 10 thousand newborns. According to WHO, persons with Alport syndrome make up 1% of all patients with kidney dysfunction. According to ICD-10, the disease has the code Q87.8.

In Alport's syndrome, the gene encoding the structure of the collagen protein located in the basement membrane of the renal tubules, inner ear and organ of vision is affected. The main function of the basement membrane is to support and separate tissues from each other. Hereditary non-immune glomerulopathy is manifested by hematuria, sensorineural hearing loss, visual impairment. As the syndrome progresses, patients develop renal failure, which is accompanied by diseases of the eyes and ears. The disease is progressive and untreatable.

Hereditary nephritis or familial glomerulonephritis are names for the same pathology. It was first described in 1927 by British scientist Arthur Alport. He followed members of one family who suffered from hearing loss and had red blood cells in urine tests. A few years later, eye lesions were detected in individuals with this disease. And only in 1985, scientists established the cause of such anomalies. It was a mutation of the gene responsible for the synthesis and structure of type IV collagen.

Most often, this ailment causes severe renal dysfunction in males. Women can pass the mutant gene on to their children without any clinical symptoms. The syndrome manifests from the first years of life. But most often found in babies aged 3-8 years. Affected children first show signs of kidney damage. Hearing and vision problems develop somewhat later. In late childhood and adolescence, a severe pathology of the kidneys, loss of vision and hearing is formed.

According to the mode of inheritance of anomalies, 3 forms of pathology are distinguished: X-linked dominant, autosomal recessive, autosomal dominant. Each form corresponds to certain morphological and functional changes in the internal organs. In the first case, the classical form develops, in which inflammation of the kidney tissue is manifested by blood in the urine and is accompanied by a decrease in hearing and vision. In this case, the disease has a progressive course, kidney failure develops rapidly. The histological feature of such processes is the thinning of the basement membrane. In the second case, the congenital ailment is much easier and is characterized by isolated inflammation of the kidneys with hematuria. The autosomal dominant form is also considered benign, has a favorable prognosis, and is manifested only by hematuria or is asymptomatic.

Detect hereditary inflammation of the kidneys by chance, during a physical examination or diagnostic examination of other diseases.

Etiology

The true etiopathogenetic factors of pathology are still not fully understood. It is believed that Alport syndrome is a hereditary disease caused by a mutation of a gene located on the long arm of the X chromosome and encoding type IV collagen protein. The main function of collagen is to ensure the strength and elasticity of connective tissue fibers. With this syndrome, damage to the vascular wall of the kidneys, the organ of Corti, and the lens capsule is noted.

The mutant gene is most often passed from parents to children. There are main forms of inheritance of pathology:

• The dominant X-linked type of inheritance is characterized by the transmission of the affected gene from the mother to the son or daughter, and from the father only to the daughter. The syndrome is more severe in boys. Sick fathers produce healthy sons and sick daughters.
• The autosomal recessive type is characterized by receiving one gene from the father, and the second from the mother. Sick children are born in 25% of cases, and equally often among both girls and boys.

In a family with hereditary diseases of the urinary system, the probability of having sick children increases significantly. If a sick child is born in a family where all members have perfectly healthy kidneys, the cause of the syndrome is a spontaneous genetic mutation.

Factors contributing to the development of the disease:

1. relatives with kidney pathologies;
2. family marriages;
3. shifts in the immune system;
4. hearing loss at a young age;
5. acute infections of bacterial or viral origin;
6. vaccination;
7. physical stress.

Expression of the mutant gene in different individuals varies from mild to severe clinical manifestations of hereditary nephritis. The process of destruction of the basement membrane is directly dependent on the severity of the pathological process.

Pathogenesis

Pathogenetic links of the syndrome:

• violation of collagen biosynthesis or its deficiency,
• destruction of the basement membrane of the kidneys, inner ear and eye apparatus,
• germination of collagen fibers of types V and VI,
• glomerular injury,
• immunonegative glomerulitis,
• glomerular hyalinosis, tubular atrophy and renal stromal fibrosis,
• glomerulosclerosis,
• accumulation of lipids and lipophages in the renal tissue,
• a decrease in the blood level of Ig A, an increase in IgM and G,
• decreased activity of T- and B-lymphocytes,
• violation of the filtration function of the kidneys,
• dysfunction of the organ of vision and hearing,
• accumulation of toxins and metabolic products in the blood,
• proteinuria,
• hematuria,
• development of acute renal failure,
• death.

The disease develops gradually with renal symptoms. In the early stages of the pathology, the kidneys work fully, there are traces of protein, leukocytes and blood in the urine. Pollakiuria and nocturia are accompanied by hypertension and other signs of urinary syndrome. In patients, the calyces and pelvises of the kidneys expand, aminoaciduria occurs. After some time, hearing loss of neurogenic origin joins.

Men are most prone to developing kidney dysfunction. If untreated, death occurs at the age of 15-30 years. Women usually suffer from a latent form of pathology with signs of hematuric syndrome and a slight hearing loss.

Symptoms

Hereditary nephritis in children can proceed according to the glomerulonephrotic or pyelonephrotic type. Clinical signs of Alport's syndrome are conditionally divided into two large groups - renal and extrarenal.

The main manifestations of renal symptoms are: hematuria - blood in the urine and proteinuria - protein in the urine. Erythrocytes in the urine of sick children appear immediately after birth. At first it is asymptomatic microhematuria. Closer to 5-7 years, the blood in the urine becomes clearly visible. This is a pathognomonic sign of Alport's syndrome. The intensity of hematuria increases after acute infectious diseases - SARS, chicken pox, measles. Active physical activity and preventive vaccinations can also provoke a significant increase in red blood cells. Somewhat less often, boys develop proteinuria. In girls, this symptom is usually absent. The loss of protein in the urine is accompanied by edema, increased blood pressure, and general intoxication of the body. Possible leukocyturia without bacteriuria, anemia.

Developing, Alport's disease is complicated by the development of renal failure. Its classic signs are dry, yellowish skin, decreased turgor, dry mouth, oliguria, hand tremors, aching muscles and joints. In the absence of proper treatment, the terminal stage of pathology occurs. In such cases, only hemodialysis will help maintain the vitality of the body. Timely replacement therapy or transplantation of a diseased kidney can prolong the life of patients.

Extrarenal symptoms include:

1. hearing loss caused by neuritis of the auditory nerve;
2. visual impairment associated with cataracts, changes in the shape of the lens, the appearance of white or yellow blotches on the retina in the macula, myopia, keratoconus;
3. delay in psychophysical development;
4. congenital defects - high palate, syndactyly, epicanthus, deformity of the ears, malocclusion;
5. leiomyomatosis of the esophagus, trachea, bronchi.

Nonspecific general intoxication signs of pathology include:

• headache,
• myalgia,
• dizziness,
• sharp fluctuations in blood pressure,
• dyspnea,
• fast, shallow breathing
• noise in ears,
• skin pallor,
• frequent urge to urinate
• dyspepsia,
• loss of appetite
• disruption of sleep and wakefulness,
• itchy skin,
• convulsions,
• chest pain,
• confusion.

Patients develop compensated glomerular and tubular insufficiency, impaired transport of amino acids and electrolytes, the concentration ability of the kidneys, acidogenesis, and the system of nephron tubules is affected. As the pathology progresses, the signs of the urinary syndrome are supplemented by severe intoxication, asthenia and anemia of the body. Similar processes develop in boys with an affected gene. In girls, the disease is much milder, they do not develop persistent kidney dysfunction. Only during pregnancy, girls suffer from symptoms of the disease.

Complications of Alport's syndrome develop in the absence of adequate therapy. Patients develop signs of kidney failure: edema appears on the face and extremities, hypothermia, hoarseness, oliguria or anuria. Often a secondary bacterial infection joins - pyelonephritis or purulent otitis develops. In this case, the prognosis is unfavorable.

Diagnostics

Alport syndrome is diagnosed and treated by pediatricians, nephrologists, geneticists, ENT doctors, and ophthalmologists.

Diagnostic measures begin with the collection of an anamnesis and listening to the patient's complaints. The family history is of particular importance. Specialists find out whether there were cases of hematuria or proteinuria in relatives, as well as deaths from kidney dysfunction. Data from genealogical analysis and obstetric history are important for making a diagnosis.

1. A specific lesion of the basement membrane in patients is detected by the results of a biopsy.
2. In the general analysis of urine - erythrocytes, protein, leukocytes.
3. Genetic research - detection of gene mutations.
4. Audiometry detects hearing loss.
5. Examination by an ophthalmologist reveals a congenital pathology of vision.
6. Ultrasound examination of the kidneys and ureters, magnetic resonance imaging, x-rays and scintigraphy are additional diagnostic techniques.

Treatment

Alport syndrome is an incurable disease. The following recommendations of experts will help slow down the development of kidney failure:

• Rational and vitaminized nutrition,
• Optimal physical activity
• Frequent and long walks in the fresh air,
• Sanitation of foci of chronic infection,
• Prevention of infectious diseases,
• Prohibition of standard vaccinations for sick children,
• Phytocollection of nettle, yarrow and chokeberry is indicated for sick children with hematuria,
• Vitamin therapy and biostimulants to improve metabolism.

Proper nutrition is the use of easily digestible foods with a sufficient content of essential nutrients. Salinity and smoked meats, spicy and spicy dishes, alcohol, products with artificial dyes, stabilizers, flavors should be excluded from the diet of patients. In case of impaired renal function, it is necessary to limit the intake of phosphorus and calcium. Such recommendations should be followed by patients throughout their lives.

Medical symptomatic therapy:

1. To eliminate hypertension, ACE inhibitors are prescribed - Captopril, Lisinopril and angiotensin receptor blockers - Lorista, Vasotens.
2. Pyelonephritis develops as a result of infection. In this case, antibacterial and anti-inflammatory drugs are used.
3. To correct violations of water-electrolyte metabolism, Furosemide, Veroshpiron, intravenous saline, glucose, calcium gluconate are prescribed.
4. Anabolic hormones and iron-containing drugs are indicated for the accelerated formation of red blood cells.
5. Immunomodulatory therapy - Levamisole.
6. Antihistamines - Zirtek, Cetrin, Suprastin.
7. A complex of vitamins and drugs that improve metabolism.

Hyperbaric oxygen therapy has a positive effect on the severity of hematuria and kidney function. With the transition of renal failure to the terminal stage, hemodialysis and kidney transplantation are required. Surgery is performed after the patient reaches the age of fifteen. Recurrence of the disease in the graft is not observed. In some cases, the development of nephritis is possible.

Gene therapy for the syndrome is currently being actively developed. Its main goal is to prevent and slow down the deterioration of kidney function. This promising treatment option is now being introduced into medical practice by Western medical laboratories.

Forecast and prevention

Alport syndrome is a hereditary disease, which is simply impossible to prevent. Compliance with all doctor's prescriptions and maintaining a healthy lifestyle will help improve the general condition of patients.

The prognosis of the syndrome is considered favorable if patients have hematuria without proteinuria and hearing loss. Renal failure also does not develop in women without damage to the auditory analyzer. Even in the presence of persistent microhematuria, their disease practically does not progress and does not worsen the general condition of patients.

Hereditary nephritis, combined with the rapid development of renal failure, has a poor prognosis in boys. They develop early kidney, eye, and ear dysfunctions. In the absence of timely and competent treatment, patients die at the age of 20-30 years.

Alport syndrome is a dangerous disease that, without the provision of qualified medical care, worsens the quality of life of patients and ends in their death. To alleviate the course of hereditary nephritis, it is necessary to strictly follow all medical recommendations.

Video: lecture on Alport syndrome

In the last few centuries, scientific and technological progress has been widely developed, massive factories, factories and enterprises are being created. The release of various toxins into the atmosphere, water bodies and soil often leads to the development of congenital diseases. One of the rare ailments of this kind is Alport's syndrome - a pathology that affects several systems of the human body at once (especially the kidneys and sensory organs suffer). It is quite difficult to fight this form of the disease, and there is also a high probability of its transmission to subsequent generations.

Definition of Alport Syndrome

Alport syndrome is a congenital disease associated with the occurrence of pathological mutations in the body. As a result, the formation of abnormal collagen occurs, which disrupts the functioning of organs or tissues. The source of the mutated gene may be one of the parents of the child (more often the disease is transmitted from the mother). Pathology is extremely rare (less than 15 people per 100,000 population).

The triad typical of Alport syndrome is found in 50% of cases

Since the development of the disease is mainly affected by people of the same kindred group, it can be called hereditary nephritis. It is believed that the likelihood of developing an ailment increases with incest.

What types of pathology exist:

• isolated damage to the renal glomeruli;
• the presence of hearing loss or deafness in combination with kidney damage and visual impairment;
• deafness, myopia, nephritis and external deformities;
• asymptomatic carrier.

Reasons for the development of the disease

At the heart of the formation of all symptomatic manifestations of the disease is a gene mutation. In the human body, a failure occurs at the molecular level, as a result of which the normal assembly and transportation of collagen, a protein that is part of almost all organs and tissues of the human body, is disrupted. The disease is hereditary and can be transmitted to the patient from his ancestors in the following ways:

• autosomal dominant (occurs in a person, even if only 1 of his parents suffered from an illness);
• autosomal recessive (occurs in a child when the mother and father have the same genetic mutations);
• sex-linked (a woman is an asymptomatic carrier, and a man develops the entire clinical picture of the disease).

Exacerbation and manifestation of Alport's syndrome occur when exposed to the following factors:

• transferred ARVI, flu, colds;
• surgical intervention;
• traumatic damage to various organs and tissues;
• stress and mental stress;
• vaccination against infections;
• pregnancy, childbirth, the formation of menstrual function;
• use of drugs, alcohol and nicotine;
• uncontrolled intake of drugs.

Clinical manifestations of Alport syndrome

Symptoms of this disease in 80% of patients appear in the first 10 years of life. When carrying mutant genes, people may not even be aware that they have such an ailment, since its typical picture is completely absent. Due to the different clinical forms of Alport syndrome, it is impossible to clearly distinguish the leading symptom of the disease, several symptoms are observed at once:

1. Reduced vision. The patient notes that in low light, the clarity of the letters disappears, the image begins to blur and get lost. This is directly related to the change in the collagen fibers that make up the lens of the eye. Initially, it is possible to correct this problem with the help of glasses and lenses, but subsequently the patient may need surgery.
2. Hearing loss or complete deafness. Most often, the appearance of this symptom is noticed by friends and relatives: the patient constantly adds sound, cannot perceive whispered speech, he begins to speak louder. Both ears are affected, as a result of which the patient cannot perceive low and high frequencies. Patients may also complain of increasing noise inside the head that interferes with concentration.
3. The appearance in the urine of foreign impurities. When the kidneys are damaged during Alport syndrome, vascular damage develops, resulting in the formation of blood in the urine. First, single erythrocytes are detected, with the progression of the disease, the urine is completely stained, massive clots appear. With an unfavorable course of the disease, a blockage of the ureter or pelvis occurs, as a result of which the passage of urine is disturbed.
4. Pain in the lumbar region. Unpleasant pressing and pulling sensations are aggravated by physical exertion, stress, inflammatory diseases, and taking certain medications. Their occurrence is associated with deformation of the renal substance due to edema.
5. Drops in blood pressure. Patients often complain of shingles headaches that occur after eating salty, fatty foods or alcohol. This symptom is a sign of the development of arterial hypertension that accompanies kidney damage. And also for patients with Alport's syndrome, collapse is typical - relaxation of peripheral vessels, as a result of which pressure drops sharply and the victim loses consciousness.

Various methods of confirming the diagnosis

A patient with a progressive decrease in hearing, vision and problems with the urinary system most often turns to a therapist. In the presence of all three main signs of the disease, it is not difficult to immediately make a diagnosis. However, in the absence of one or more of them, it is much harder to decide. Alport's syndrome is differentiated from:

• sensorineural hearing loss;
• labyrinth deafness;
• myopia;
• cataract;
• pyelonephritis;
• glomerulonephritis;
• malignant or benign kidney tumor.

The following methods are used to confirm the diagnosis:

• a general urine test - the appearance of protein, red blood cells and a change in the turbidity of the urine make it possible to suspect kidney problems;
• ultrasound diagnostics reveals pathological edema of the glomeruli and a violation of their structure;
• a progressive decrease in the frequency of hearing is recorded using tympanometry (the elasticity of the eardrum is determined);
• myopia is detected by an ophthalmologist using special tables and apparatus (a decrease in visual acuity is a clear symptom of the disease);
• molecular genetic typing of biological material (mutations are detected in the human genome responsible for the formation of pathological collagen).

Alport syndrome is a rather rare disease that is difficult for a young doctor to suspect. One of my patients went through a long journey through various authorities before being diagnosed. At the age of 6, he was diagnosed with progressive hearing loss, after which the child was sent to an ENT doctor. He confirmed the diagnosis and prescribed a hearing aid for permanent wear. During a vision test before entering grade 1, the baby was found to have severe myopia that could not be corrected with glasses. In adolescence, the boy began to get sick often and constantly experienced kidney problems, which doctors mistakenly took for manifestations of pyelonephritis after the flu or tonsillitis. For several months, the patient was treated with antibiotics, and his condition steadily worsened. Only after that, the doctors decided to conduct a genetic study, which revealed the presence of a collagen protein mutation. The boy was selected a suitable course of therapy, after which he felt better and the opportunity to perform a kidney transplant operation appeared.

How is Alport syndrome treated?

Tactics after confirming the diagnosis of the disease directly depends on the severity of the patient's condition. If he does not have visible clinical manifestations of renal failure and intoxication of the body, treatment is carried out at home or in a day hospital, where a person must regularly come for pharmaceuticals. With a more severe course of the disease, hospitalization in the department of nephrology or urology is indicated. Drug therapy is aimed at eliminating the main symptoms of Alport syndrome, as well as protecting against damage to the kidney tissue. In the absence of the effect of conservative treatment, hemodialysis is prescribed, and after it - a kidney transplant operation. The patient must always observe the ward regimen and adhere to the diet.

The main goals of therapy for Alport syndrome:

• prevention of progression of renal failure;
• normalization of water-salt balance;
• protection against microbial infection;
• strengthening immunity;
• removal of harmful toxins from the body.

Table: used medications

Name of the drug group	Main active ingredients	Effects of use
Steroid anti-inflammatory drugs	Etodolac; Diclofenac; Ibuklin; ibuprofen; Tamoxifen.	Reduce the severity of unpleasant pain in the lower back and lumbar region, relieve swelling of the kidney tissues
Non-steroidal anti-inflammatory drugs	Hydrocortisone; Cortef; Laticort; Methylprednisolone; Dexon; Dexamethasone.
Immunostimulants	Immunal; Timalin; Thymogen; Taktivin; Cycloferon.	Contribute to the formation of protective cells in the bone marrow, which ensure the functioning of the immune system
Diuretics	Spironolactone; Hypothiazide; Torasemide; Mannitol.	They remove excess fluid and toxic substances from the body that accumulate during insufficient kidney function, normalize blood pressure
Vitamin and mineral complexes	Aevit; Calcium D3-Nycomed; Suprastin; Alphabet.	Restore the balance of essential trace elements that are involved in metabolic processes

Photo gallery: means for drug therapy of the disease

Furosemide removes excess fluid from the body
Nimesulide has an analgesic effect Polyoxidonium strengthens the immune system

A patient with kidney disease must constantly follow a diet. With Alport syndrome, the normal absorption of nutrients is disrupted, and various toxins are not removed from the body. To combat the symptoms of the disease, a huge amount of energy is spent, which must be restored with the help of food. The balance of proteins, fats and carbohydrates should be 4:1:1. It is necessary to add more vitamins of groups B, C and A to the diet, as well as trace elements sodium, potassium, calcium and magnesium. It is recommended to cook only with fresh produce purchased from a farmers' market or from private sellers to avoid preservatives and harmful additives.

Patients with Alport syndrome need to regularly monitor the amount of water consumed. More than 2 liters during the day create an extra burden on the kidneys.

Approximate food menu for patients:

1. Breakfast. Omelet with goat cheese and greens, some toast with butter and ham. It is recommended to replace coffee with red tea so as not to provoke an increase in blood pressure. As an alternative to scrambled eggs, various cereals with milk or cottage cheese with fruit can be used.
2. Dinner. Soup cooked on lean beef, chicken or turkey (borscht, pea, cabbage soup, pickle, kharcho), as well as sea or sauerkraut salad. If necessary, you can eat a few slices of black bread with garlic or onions to strengthen immunity.
3. Dinner. Lean cutlets, boiled chicken or fish with a minimum amount of salt. For garnish, you can use durum pasta, stewed vegetables (it is recommended to limit the use of potatoes), rice, buckwheat, lentils, chickpeas, beans.

Photo gallery: healthy food

Curd is the best source of calcium Vegetables and fruits are rich in vitamins Cereals - a source of slow carbohydrates

Physiotherapy techniques to combat the symptoms of the disease

At the recovery stage, it is necessary to strengthen the patient's body and protect it from the development of secondary complications. Physiotherapy procedures, which are based on the application of physical phenomena, perfectly cope with these tasks. The course of treatment is selected by a nephrologist based on data on the course of the disease. With an exacerbation of Alport's syndrome, it is recommended to cancel some procedures, as they will cause more harm to the body than good.

Physiotherapeutic methods for the treatment of pathology:

1. UHF therapy is based on the use of high frequency electric fields. This method helps to get rid of discomfort in the lumbar region, and also relaxes spasmodic muscles.
2. Massage is prescribed in the absence of data on the prolapse of the kidneys. Acupressure on soft tissues improves blood circulation and lymph outflow, which protects the body from the addition of undesirable complications in the form of venous congestion.
3. laser therapy. Directed beams reduce the intensity of inflammation, and also prevent the formation of pathological growths of connective tissue (adhesions).
4. The use of ultrasound promotes faster regeneration of soft tissues and ensures the healing of minor injuries.

Photo gallery: physiotherapy to combat the disease

The use of a laser protects against the development of adhesions
UHF therapy effectively copes with the symptoms of the disease Ultrasound therapy stimulates regeneration

Surgical techniques to eliminate the consequences of the disease

In Alport's syndrome, kidney tissue is affected (especially the tubular system). The organ loses its ability to perform its usual functions, as a result of which it needs to be replaced. The selection of a donor is carried out on the basis of many criteria (the next of kin are not suitable due to the likelihood of a latent form of the disease) and takes up to several years. Transplantation is performed in patients from 5–6 years of age.

The operation goes through the following steps:

1. Treatment of the surgical field. The lumbar region is covered with sterile wipes and wiped with alcohol and iodine.
2. The doctor makes an incision, successively pushing the skin, fatty tissue and muscle bundles apart. The damaged kidney and its pedicle, including vessels, ureter and nerve bundles, are removed from the wound. In parallel with this, other medical workers prepare the graft.
3. The new kidney is placed slightly higher than the previous one, after which it is sutured and fixed to the surrounding tissues. The changed old organ is not removed so that it also continues to perform at least part of its functions.
4. Consistent connection of skin, fatty tissue and muscle bundles. A rubber tube remains in the wound area - drainage, through which pathological contents (pus, blood) flow. The operated patient is transferred to the intensive care unit for observation.

Remember that a donor kidney transplant will not help you get rid of Alport syndrome. In my practice, I met a patient who, after the operation, drastically changed his usual way of life, began to actively drink alcohol and smoke several cigarettes during the day, and stopped taking the necessary medications. This led to a sharp deterioration in his condition, the man was hospitalized in the intensive care unit, as the transplanted kidney began to be rejected. At the cost of incredible efforts, the doctors managed to leave the transplant and prevent its infection. That is why even after the operation, it is necessary to monitor your health and take medication.

Hemodialysis for Alport's syndrome

With a long-term violation of kidney function, toxins accumulate in the body, which are difficult to remove without outside intervention. Hemodialysis is used to protect the brain, nervous system, and other important organs from damage. This procedure is aimed at extrarenal blood purification from harmful impurities (chemical elements, decay products of harmful substances, various microbes) and is indicated for all patients with moderate Alport syndrome. Hemodialysis is prescribed in the following situations:

• a threatening increase in the level of creatinine and urea;
• severe impairment of kidney function;
• failure of one of the organs.

The treatment consists in the mechanical purification of the blood

The patient is on a reclining couch, after which special catheters and tubes are inserted into the cubital vein. Through them, blood flows into the apparatus, which passes fluid through elastic membranes. Thus, the bloodstream is cleared of toxins and foreign impurities, since they do not pass through the pores of the filter. Repeat this treatment as needed (at least 1 time in 6 months).

During hemodialysis, the patient is provided with a certificate or sick leave for all the hours that the procedure requires. Patients practically do not experience discomfort and can safely go about their business. Patients in my department prefer to spend time reading books, watching movies or series, word games. This helps to create a comfortable psychological environment.

Predictions and undesirable consequences of the disease

Alport syndrome is an incurable hereditary pathology that is passed on to the next generation with the genes of one or both parents. A complete cure cannot be achieved even after a kidney transplant operation. All therapy is aimed at maintaining the patient's well-being at the desired level and protecting against the development of complications. The life expectancy of patients with this diagnosis is reduced by 10-15 years. The likelihood of developing undesirable consequences is influenced by the age of the patient, the presence of other acute or chronic ailments, injuries and infections, as well as lifestyle and compliance with medical recommendations.

When a disease is detected in children, an individual program of training and monitoring of health indicators is created for each baby, which makes it possible to avoid undesirable consequences.

While working in the Department of Nephrology, I had the opportunity to encounter a man aged 65 who was diagnosed with Alport syndrome in childhood. The patient did not have any characteristic external changes, and all tests were extremely good. During the survey, it was found that the patient leads a predominantly healthy lifestyle, regularly vaccinated against influenza, eats food in accordance with the diet, engages in light physical activity, does not smoke or drink alcoholic beverages. This attitude of the man to treatment allowed him to avoid a kidney transplant operation, as well as to refuse from hemodialysis for a long time.

Possible complications and undesirable consequences that may occur in patients with Alport syndrome:

• chronic or acute renal failure;
• creation of conditions for the accession of a secondary infection;
• immunodeficiency states;
• destruction of one or both kidneys;
• accumulation in the body of toxic substances that are not excreted in the urine;
• social maladaptation;
• progressive deterioration of hearing and vision;
• increased risk of developing malignant neoplasms;
• anemia - a decrease in the level of hemoglobin and red blood cells in the blood;
• inflammatory diseases of the kidneys;
• disorders of mental and physical development (in children).

Features of the clinical picture and treatment of Alport syndrome in children

You can suspect the presence of a pathology in a baby immediately after his birth. Children have characteristic changes and deformities of the facial skull in the form of a splitting of the upper lip (cleft lip) and a funnel-shaped hard palate (cleft palate), increased head size, as well as a typical facial expression with a wandering look. Other mutations can manifest as hearing and visual impairment. Such a child does not even react to loud sounds and sudden movements of the environment, which is found even in the maternity hospital.

To eliminate external defects, small patients undergo plastic surgery. I happened to participate in the suturing of the upper lip of a child with such a problem. After surgery, a small scar remains, which fades over time and becomes almost invisible. Operations are performed within a few weeks after the birth of the child, which reduces the risk of secondary complications.

To prevent damage to the kidney tissue, small patients are prescribed a special diet. Newborns and infants are breastfed or receive a mixture that is maximally adapted to the composition of human milk. This eliminates the risk of developing an immune deficiency. The main means for the treatment of symptomatic signs of the disease are introduced at 5–7 years of age (earlier - as needed) and practically do not differ from the treatment that an adult receives. For the adaptation of blind and deaf children in society, hearing aids are used, corrective operations. For the first few years, the child must attend special schools or additionally study with a specialist in order to catch up with peers.

Photo gallery: what children with Alport syndrome look like

A change in the shape of the skull during the disease occurs in 40% of cases Puffiness of the face is a result of improper functioning of the kidneys. External defects help to immediately suspect the presence of an ailment

Features of the development of the disease in girls and the impact on reproductive function

In female patients, there are not always clear signs of Alport syndrome. Many girls learn about the carriage of such a pathology only after the birth of a sick baby. In more severe cases, the disease is activated during puberty under the influence of hormonal changes in the body (during menstruation) or after the first sexual experience.

If the patient's condition is stable, and there are no other contraindications (damage to a single kidney, recent surgery), you can have a baby.

In my practice, there was a patient in whom Alport's syndrome appeared every 3 generations. In this patient, the pathology was dormant for a long time, but became more active after the stress. The woman noted that her great-grandmother and sister also suffered from this form of the disease. Doctors calculated that the likelihood of such a disease appearing in subsequent generations is extremely high.

Patients with a severe form of Alport's syndrome experience certain difficulties in conceiving and bearing a child. This may be due both to abnormalities in the structure of the reproductive organs, and to disruption of the endocrine system. During the period of growth and development of the fetus, the mother's body produces 2 times more fluid, as a result of which the load on the kidneys increases significantly. Due to nephritic changes of an inflammatory nature, the body cannot cope with an increase in the volume of circulating blood, and a woman has miscarriages at various times.

What complications can occur in patients with Alport syndrome during pregnancy:

Hereditary kidney diseases are a group of dangerous pathologies that significantly reduce not only the quality of human life, but also its duration. Currently, the problem of early diagnosis of Alport's syndrome is especially relevant. Almost all patients live in ignorance for many years, until some abrupt factor provokes the development of clinical symptoms of the disease and its complications. That is why it is so important to constantly monitor your health, noting the slightest changes in well-being, and also regularly contact the doctor to monitor the tests.

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. The 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.

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.

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

- a hereditary kidney disease caused by a change in the synthesis of type IV collagen, which forms the basement membranes of the renal glomeruli, the structure of the inner ear, and the lens of the eye. Men suffer from an advanced form of the disease with severe symptoms. Women are often carriers of the gene, remaining healthy, or their manifestations of the disease are mild. The main symptoms are microhematuria, proteinuria, renal failure, sensory hearing loss, deformity and dislocation of the lens, cataracts. The diagnosis is established according to clinical and anamnestic data, the results of a general urinalysis, kidney biopsy, audiometry and ophthalmological examination. Treatment is symptomatic, including ACE inhibitors and ARBs.

ICD-10

Q87.8 Other specified congenital anomaly syndromes, not elsewhere classified

General information

Familial cases of hematuric nephropathy first came to the attention of researchers in 1902. Almost 30 years later, in 1927, the American physician A. Alport discovered the frequent association of hematuria with hearing loss and uremia in men, while women had no or mild symptoms. He suggested the hereditary nature of the disease, which was later named Alport's syndrome. Synonyms -, hematuric nephritis, familial glomerulonephritis. The prevalence is low - 1 case per 5 thousand people. Pathology accounts for 1% of patients with renal failure, 2.3% of patients undergoing kidney transplantation. The disease is diagnosed in people of all races, but the ratio of different forms is not the same.

Causes

By its nature, the syndrome is a heterogeneous hereditary disease - its development is provoked by a defect in the genes that encode the structure of the various chains of type IV collagen. Genetic changes are represented by deletions, splicing, missense and nonsense mutations. Their localization determines the type of inheritance of the disease:

• X-linked dominant. It is associated with a mutation in the COL4A5 locus, which is located on the X sex chromosome. The gene encodes the a5-chain of type 4 collagen. This genetic defect causes 80-85% of cases of hereditary nephritis. The disease is fully manifested in boys and men; in females, the remaining normal gene on the X chromosome compensates for the production of functional collagen.
• Autosomal recessive. It develops on the basis of mutations in the C0L4A3 and COL4A4 genes. They are localized on the second chromosome and are responsible for the structure of the a3 and a4 collagen chains. Patients with this variant of the syndrome make up about 15% of patients. The severity of symptoms does not depend on gender.
• Autosomal dominant. Nephritis results from mutations in the COL4A3-COLA4 genes located on chromosome 2. As in the case of the autosomal recessive form of the disease, the synthesis of a4 and a3 collagen chains of the fourth type is disrupted. The prevalence is 1% of all cases of genetic nephritis.

Pathogenesis

The glomerular basement membrane has a complex structure, it is formed by a strict geometric sequence of type 4 collagen molecules and polysaccharide components. In Alport syndrome, there are mutations that determine the defective structure of the helical collagen molecules. At the first stages of the disease, the basement membrane becomes thinner, begins to split and exfoliate. At the same time, thickened areas with uneven enlightenments appear. A fine-granular substance accumulates inside. The progression of the disease is accompanied by complete destruction of the basal glomerular membrane of the glomerular capillaries, tubules of the kidneys, structures of the inner ear and eyes. Thus, Alport's syndrome is pathogenetically represented by four links: a gene mutation, a defect in the structure of collagen, destruction of basement membranes, and kidney pathology (sometimes hearing and vision impairment).

Symptoms

The most common manifestation of Alport syndrome is hematuria. Microscopically, this symptom is determined in 95% of women and 100% of men. During routine examination of boys, hematuria is detected already in the first years of life. Another common symptom of the disease is proteinuria. The excretion of protein in the urine in male patients with X-linked syndrome begins in early childhood, in the rest - later. In girls and women, the level of protein excretion increases slightly, cases of severe proteinuria are extremely rare. All patients have a steady progression of the symptom.

Often, patients develop sensorineural hearing loss. Hearing impairment makes its debut in childhood but becomes noticeable in adolescence or early adulthood. In children, hearing loss applies only to high-frequency sounds, it is detected in specially created conditions - with audiometry. As the syndrome matures and progresses, the auditory perception of medium and low frequencies, including human speech, is impaired. With X-linked syndrome, hearing loss is present in 50% of male patients by the age of 25, and in 90% by the age of 40. The severity of the hearing loss is variable, from changes in the audiogram results alone to total deafness. There are no pathologies of the vestibular apparatus.

Visual disturbances include anterior lenticonus - protrusion of the center of the lens of the eye forward and retinopathy. Both pathologies are manifested by a progressive deterioration in visual function, redness, and pain in the eyes. Some patients have dysembryogenesis stigmas - anatomical anomalies of the urinary system, eyes, auricles, limbs. There may be a high location of the sky, shortening and curvature of the little fingers, fusion of the toes, widely spaced eyes.

Complications

The lack of treatment of patients with Alport's syndrome leads to the rapid progression of deafness and blindness, the formation of cataracts. Some patients develop polyneuropathy - nerve damage, accompanied by muscle weakness, pain, convulsions, tremors, paresthesias, decreased sensitivity. Another complication is thrombocytopenia with a high risk of bleeding. The most dangerous condition in hereditary nephritis is the end-stage renal failure. Men with the type of inheritance linked to the sex X chromosome are most susceptible to it. By the age of 60, 100% of patients in this group need hemodialysis, peritoneal dialysis, and donor kidney transplantation.

Diagnostics

Nephrologists, urologists, internists and geneticists take part in the diagnostic process. During the survey, the age of onset of symptoms, the presence of hematuria, proteinuria, or deaths due to chronic renal failure in first-line relatives are found out. Alport syndrome is characterized by an early onset and a burdened family history. Differential diagnosis is aimed at excluding the hematuric form of glomerulonephritis, secondary nephropathies. To confirm the diagnosis, the following procedures are carried out:

1. Physical examination. Pallor of the skin and mucous membranes, reduced muscle tone, external and somatic signs of dysembryogenesis - high palate, anomalies in the structure of the limbs, increased distance between the eyes, nipples are determined. In the early stages of the disease, arterial hypotension is diagnosed, in the later stages - arterial hypertension.
2. General urine analysis. Erythrocytes and increased protein content are found - signs of hematuria and proteinuria. The indicator of urine protein directly correlates with the severity of the syndrome; the progression of the pathology, the likelihood of nephrotic syndrome, and chronic renal failure are assessed by its change. There may be signs of leukocyturia of an abacterial nature.
3. Examination of a kidney biopsy. Microscopy visualizes a thinned basement membrane, splitting and separation of its layers. At the late stage, there are thickened dystrophic areas with "honeycombs" of enlightenment, zones of complete destruction of the layer.
4. Molecular genetic study. Genetic diagnostics is not mandatory, but it allows you to make a more accurate prognosis, choose the optimal treatment regimen. The structure of genes, mutations in which cause the development of the syndrome, is being studied. Most patients have mutations in the COL4A5 gene.
5. Audiometry , ophthalmological examination . Additionally, patients can be assigned diagnostic consultations of an audiologist and an ophthalmologist. Audiometry reveals hearing loss: in childhood and adolescence - bilateral high-frequency hearing loss, in adulthood - low-frequency and mid-frequency hearing loss. The ophthalmologist determines the distortion of the lens shape, retinal damage, the presence of cataracts, decreased vision.

Alport Syndrome Treatment

There is no specific therapy. From an early age, active symptomatic treatment is carried out, which reduces proteinuria. It helps prevent damage and atrophy of the renal tubules, the development of interstitial fibrosis. With the help of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, it is possible to stop the progression of the disease, to achieve regression of glomerulosclerosis, tubulointerstitial and vascular changes in the kidneys. Patients with end - stage chronic renal failure are prescribed hemodialysis , peritoneal dialysis , and the question of the advisability of kidney transplantation is being decided .

Forecast and prevention

The syndrome is prognostically favorable in cases where hematuria occurs without proteinuria, there are no visual disturbances and hearing loss. In addition, the prognosis is good in most women - even in the presence of hematuria, the disease progresses slowly, does not worsen the general condition. Due to the hereditary nature of the pathology, it is impossible to prevent its development. In families where the presence of the X-linked form of the syndrome has been established, prenatal diagnosis is possible. Genetic screening is especially recommended for women who are carrying boys.

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 hereditary nephritis has been pointed out.

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 have families 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.

Collagen type IV, 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 basal membranes in the later stages of the disease, with the growth of type V and VI collagen in them, which manifests itself 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

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

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 appear to 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.

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.

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.