Alport Syndrome - Symptoms, Diagnosis, and Treatment of Alport Syndrome

Alport syndrome is an inherited disorder that causes impaired kidney function. As a result of this impaired kidney function, the disease usually progresses to kidney failure. It is notable that this disease primarily affects boys and men, while girls and women are affected less frequently. The name “Alport syndrome” comes from the South African physician Arthur Cecil Alport, who discovered the disease in the 1920s.

Alport syndrome cannot be stopped; ultimately, the patient must expect to undergo dialysis or hope for a donor kidney for a kidney transplant. However, the progression of kidney failure can be delayed with medication.

Alport syndrome can manifest in various ways. For example, this condition can cause discoloration of the urine due to blood or increased protein deposits in the urine. Urine may also take on an abnormal color due to infections or other illnesses. In such cases, it may appear pink or even brownish. This is generally harmless, as the urine will return to its normal color once the infection or illness has been successfully treated.

Alport syndrome is also characterized, for example, by problems with the inner ears or the eyes. The reason: Alport syndrome involves mutations in what is known as type IV collagen. This collagen is found in the eyes and inner ears, which is why the disease sometimes affects these areas as well. The consequences can include hearing loss or cataracts, among other things.

Other, albeit rarer, symptoms include esophageal problems, which can lead to difficulty swallowing or constipation.

Possible symptoms of Alport syndrome:

• Blood in the urine
• Elevated protein levels in the urine
• Discoloration of the urine during infections
• Hearing loss
• Eye damage

As mentioned, Alport syndrome is an inherited disorder. Therefore, if a close relative—such as a parent—already has this condition, there is a likelihood that their children will also develop it. The aforementioned mutation in type IV collagen plays a major role in Alport syndrome. It is, therefore, caused by genetic defects.

The reason why Alport syndrome primarily affects men and boys is that this genetic defect is transmitted via the X chromosome. In 50% of cases, the mother passes on the defective X chromosome to her children. Girls can compensate for the defect with the father’s healthy X chromosome, but boys do not receive a second X chromosome and therefore develop the condition.

Diagram of recessive X-linked inheritance; the genetic defect on the chromosome is marked in red

However, familial factors are not the only possible cause of the disease. Some cases are also caused by de novo mutations.

There are various diagnostic methods that enable early detection of the disease. These include, for example, an ultrasound examination of the kidneys. Kidney biopsies, blood tests, or urine tests—which examine, among other things, the protein content—can also provide information about the disease. Since the ears and eyes may also be affected, examinations of the eyes and ears are also conducted if the condition is suspected.

However, a very important factor is the family medical history. This, too, can provide valuable clues for an accurate diagnosis.

First, it should be noted that, as of the current state of medical knowledge, there is no cure for Alport syndrome. Therefore, treatment is focused solely on managing the symptoms.

The primary goal is to delay kidney failure as much as possible. This is achieved, among other things, by administering ACE inhibitors or AT antagonists. In the best-case scenario, this can delay complete kidney failure by several years. The earlier appropriate treatment is started, the better the chances of success.

Consequently, dialysis is often necessary to take over the functions of the damaged kidneys. If this treatment option reaches its limits, a donor kidney may be required.

If the eyes are affected, surgery—such as laser treatment—can lead to improvement.

What are the early signs of Alport syndrome?

Hematuria or proteinuria is often noticed early on, as the damaged basement membrane allows blood and protein to leak into the urine.

What causes Alport syndrome?

The condition is caused by a genetic mutation in type IV collagen, which is usually inherited in an X-linked manner; autosomal inheritance is less common.

How is Alport syndrome diagnosed?

The diagnosis is made through urine and blood tests, audiological or ophthalmological tests if necessary, and—for confirmation—a kidney biopsy.

What treatment options are available?

Since the syndrome is progressive, treatment aims to delay the onset of kidney failure; in later stages, dialysis or a kidney transplant may become necessary.