What is Alport Syndrome? Symptoms, Causes, and Treatment

Alport Syndrome

Alport syndrome is known as a hereditary kidney disease and generally courses together with hearing and eye problems. This syndrome results from a genetic mutation that leads to structural impairments in the glomerular basement membrane (GBM) located in the kidneys, which ensures the filtration of urine. Males exhibit more severe symptoms compared to females because the most common form shows X-linked inheritance. Placed in the group of rare diseases, Alport syndrome can lead to kidney failure over time and reduce the quality of life. Early diagnosis and regular follow-up carry great importance in terms of delaying complications.

What is Alport Syndrome?

Alport syndrome is a hereditary disease basically characterized by the deterioration of the collagen type IV structure found in the kidneys, ears, and eyes. This collagen ensures the healthy functioning of the renal glomeruli, the hearing system in the inner ear, and certain structures in the eye. Mutations occurring in the genes tasked with collagen production lead to functional impairments in these organs. The disease has three main inheritance types:

X-linked Alport syndrome

Autosomal recessive Alport syndrome (Alport syndrome type 2)

Autosomal dominant Alport syndrome

Affecting approximately one in 50,000 individuals worldwide, the initial symptoms of Alport syndrome generally begin during childhood or adolescence. These symptoms can progress over time to turn into kidney failure, hearing loss, and certain eye disorders.

What Are the Symptoms of Alport Syndrome?

Alport syndrome symptoms are generally grouped around three main systems: kidney, ear, and eye. These symptoms progress with age and can manifest with varying severity. The symptoms of Alport syndrome can be listed as follows:

Kidney Symptoms: The presence of blood in the urine (hematuria) is the earliest and most common symptom of the disease. This condition is usually at a microscopic level and is detected through urine tests. Over time, protein loss (proteinuria) begins, and kidney functions gradually deteriorate. High blood pressure develops in the majority of patients, and fluid retention (edema) is observed in body tissues. In advanced stages, kidney failure may occur.

Hearing Loss: Alport syndrome hearing loss especially begins at high-frequency sounds. This condition is generally noticed between the ages of 10-20 and progresses over time. Hearing loss develops as a result of the involvement of delicate structures in the inner ear and may necessitate the use of a hearing aid.

Eye Problems: Alport syndrome eye findings include lens deformity, retina problems, and corneal thickening. These conditions can affect visual acuity and may not be corrected with glasses. In some patients, the risk of increased intraocular pressure (glaucoma) is also present.

Alport Syndrome Appearance Characteristics and Other Symptoms: More rarely observed symptoms such as skin lesions, muscle weakness, and bone deformities may also occur. It generally has a milder course in females and sometimes manifests solely with urinary findings.

What Causes Alport Syndrome?

The fundamental cause of Alport syndrome is mutations occurring in the genes responsible for collagen type IV production in the body. These genes are named COL4A3, COL4A4, and COL4A5. The impaired collagen structure formed as a result of mutations in these genes leads particularly to the renal glomerular basement membrane (GBM) being unable to perform its normal function. Alport syndrome is also linked to a condition of enzyme deficiency. Alport syndrome is entirely a genetic disease and has three different inheritance patterns. These can be listed as follows:

X-Linked Alport Syndrome: Constituting 85% of cases, this type stems from mutations in the COL4A5 gene. Since the gene is located on the X chromosome, it has a more severe course in males. While males acquire the disease from their mothers, females generally remain in a carrier state. This type shows vertical transmission in the family, and the sisters of affected male children have a 50% probability of being carriers.

Autosomal Recessive Alport Syndrome: Constituting 10-15% of cases, this type stems from mutations in the COL4A3 and COL4A4 genes. In the event that both parents are carriers, there is a 25% risk of the disease appearing in their children. In this type, both male and female children are affected equally.

Autosomal Dominant Alport Syndrome: Being the rarest type observed, it constitutes 5% of cases. It is sufficient for only one parent to carry the disease, and there is a 50% risk of occurrence in each child. This type has a milder course.

Genetic Mechanism: Mutations occur in the genes encoding the α3, α4, and α5 chains of the type IV collagen protein. These proteins are critically important for the structural integrity of the basement membrane. Collagen IV deficiency or structural impairment causes the kidney filters, ear cochleae, and eye structures to deteriorate over time.

How is Alport Syndrome Diagnosed?

The diagnosis of Alport syndrome is made through a combination of clinical findings, laboratory tests, imaging methods, and genetic analyses. The diagnostic process requires a multidisciplinary approach. Alport syndrome diagnostic criteria can be listed as follows:

Family History and Clinical Evaluation: The initial stage of the diagnostic process is taking a detailed family history and evaluating clinical symptoms. A history of kidney disease, hearing loss, or kidney failure at a young age in the family provides important clues.

Laboratory Tests: The presence of microscopic hematuria and proteinuria is investigated in urinalysis. Kidney function indicators (creatinine, urea) are evaluated in blood tests. Complete urinalysis, 24-hour urine protein quantity, and kidney function tests are performed routinely.

Kidney Biopsy: Examining the kidney tissue with an electron microscope is very important in making the diagnosis. In this examination, typical appearances such as thickening, splitting, and basket-weave appearance can be seen in the kidney filtration membrane. Furthermore, how collagen type IV is distributed in the kidney is also checked using special stains.

Hearing Tests: The presence and degree of hearing loss are determined with an audiogram. High-frequency hearing loss is particularly investigated. Tympanometry and brainstem evoked response tests can also be performed.

Eye Examination: A detailed eye examination is performed to detect problems in the eye. Lens disorders, retina problems, and changes in the cornea are investigated in this examination. If necessary, methods such as fundus examination and optical coherence tomography can also be utilized.

Genetic Tests: Mutations in the COL4A3, COL4A4, and COL4A5 genes are investigated through molecular genetic analysis. These tests are critically important to confirm the diagnosis and provide genetic counseling.

How is Alport Syndrome Treated?

Although there is no specific treatment for Alport syndrome, various treatment approaches are applied with the aim of slowing down the progression of the disease and preventing complications. Research in the field of Alport syndrome gene therapy is also ongoing, and promising results may be obtained in the future. The following methods can be applied for Alport syndrome treatment:

Treatment Protecting Kidney Functions: ACE inhibitors and ARBs are used to reduce protein loss and protect kidney functions. These drugs can slow down the progression of the disease by lowering glomerular pressure. Blood pressure control is very important, and the target value should be kept below 130/80 mmHg.

Dialysis and Kidney Transplantation: When advanced-stage kidney failure develops, dialysis treatment may be required. Kidney transplantation is the most effective treatment option that increases the quality of life. Since there is a risk of developing anti-glomerular basement membrane disease after kidney transplantation in Alport syndrome patients, close follow-up is required.

Treatment of Hearing Loss: Hearing aids and cochlear implants are used according to the severity of hearing loss. Early intervention is critically important in terms of language development and social adaptation. Regular audiologic follow-up is required.

Treatment of Eye Problems: Glasses, contact lenses, or surgical interventions can be used to correct vision problems. Intraocular pressure-lowering treatments are applied in patients who develop glaucoma.

Lifestyle Changes: A low-salt diet, protein restriction, regular exercise, and avoiding cigarette use are recommended. Avoiding nephrotoxic drugs and protection from infections are also important.

Genetic Counseling: Genetic counseling is provided regarding family planning. Prenatal diagnosis and preimplantation genetic diagnosis options are evaluated.

Alport syndrome is a disease requiring a multidisciplinary approach. When choosing an Alport syndrome doctor, it is recommended to be followed by a team consisting of a medical genetics specialist, an ear-nose-throat specialist, and an ophthalmologist, alongside a nephrology specialist.

If you or your child has blood in the urine, decreased hearing, or similar symptoms, you can consult a nephrology or medical genetics specialist without wasting time. Thanks to early diagnosis, you can slow down the progression of the disease and increase the quality of life.

Frequently Asked Questions

Alport syndrome is a disease with genetic transmission. It most frequently passes linked to the X chromosome, and in this case, it courses more severely in males. Additionally, autosomal recessive and autosomal dominant inheritance pathways also exist. This transmission type can be determined with genetic tests, and family members can also be taken into screening. Alport affects three main organ systems primarily, which are the kidneys, inner ear, and eye. Loss of function in the kidneys, sensorineural hearing loss in the ear, and lens and retina disorders in the eye can be observed. Affected organs vary according to the type of genetic mutation. Alport syndrome can lead to progressive and usually permanent sensorineural hearing loss. Hearing loss begins during childhood or adolescence and can become severe over time. However, hearing can be supported with hearing aids or cochlear implants. Yes, Alport syndrome can severely impair kidney functions and end-stage kidney failure may develop. This process can be slowed down with early diagnosis and treatment. Dialysis or kidney transplantation may be required in advanced cases. Urine and blood tests, kidney biopsy, hearing tests, and eye examinations are performed for diagnosis. The most definitive diagnosis is made with genetic tests. Irregularities in basement membrane thicknesses can be detected in a kidney biopsy. Alport syndrome is not a disease that can be completely cured at present. However, symptoms can be brought under control, and the progression of the disease can be slowed down. Patients can live healthily for many years with appropriate treatment and lifestyle adjustments. A carrier is a person who genetically carries the disease but does not exhibit all symptoms. Females in particular can be carriers in X-linked Alport syndrome. Although findings such as mild hematuria are seen in these individuals, the disease can be transmitted to male children in a more severe manner. Occult blood in the urine (hematuria) is generally the earliest symptom in children. Furthermore, decreased hearing, a drop in school success, and eye complaints may also occur. If there is a history of Alport in the family, children should be closely monitored for these symptoms. The progression rate of the disease depends on the genetic type and personal factors. In the X-linked type in males, progression is faster, and most patients reach kidney failure around the ages of 20-30. Progression may be slower in females or in autosomally transmitted forms. If the disease has led to advanced-level kidney failure, kidney transplantation can be a permanent solution. Patients with Alport syndrome are suitable candidates for transplantation, and their quality of life generally increases after transplantation. However, the organ donor must be selected carefully.

Do You Suspect Alport Syndrome?

If you or your child has blood in the urine, hearing loss, or eye problems, consult the specialists of our Nephrology Department without wasting time. The progression of the disease can be slowed down and your quality of life can be increased with early diagnosis.

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