Alport syndrome: symptoms, inheritance, diagnosis and treatment

Kidney Research UK describes Alport syndrome as a rare genetic disorder characterised by progressive loss of kidney function, hearing loss and eye abnormalities, and the second most common cause of genetic chronic kidney disease after polycystic kidney disease. The condition is named after Arthur Cecil Alport, who described families with kidney failure and deafness in 1927, according to the National Kidney Federation (NKF).

The underlying problem is a fault in type IV collagen, a protein that gives strength to the filtering membrane in the kidneys and is also found in the inner ear and eye. The NKF explains that the gene most commonly affected is COL4A5, with COL4A3 and COL4A4 also involved.

Kidney Research UK sets out the main features. In the kidneys, blood in the urine can be present from birth, protein in the urine may develop and blood pressure may rise as kidney function declines. Visible blood can occasionally appear with minor infections.

In the ears, people usually have normal hearing at birth and in early childhood. Hearing difficulties are usually first noticed from around 5 years old and an audiogram is likely to show mild to moderate high-tone deafness, which over the next ten years is likely to slowly worsen until hearing aids are prescribed. In adult life hearing loss tends to plateau, and some useful hearing nearly always persists.

In the eyes, changes do not usually affect children but in adult life the lens may slowly become cone-shaped causing short-sightedness, white flecks may be seen at the back of the eye, though these do not affect vision, and the front of the eyes can become dry and painful.

Kidney Research UK says around 85% of Alport syndrome is X-linked, because the affected gene is on the X chromosome. A male with an affected gene will develop signs of the condition, while a female with one affected X chromosome will also develop Alport syndrome but typically with a milder condition. The remaining 15% is recessive, involving genes on chromosome 2, where males and females are equally affected.

The NKF adds that in around 15% of people with the diagnosis the genetic mutation arose in them rather than being passed from a parent, that women usually have mild disease but can pass it on with severe disease to their sons, and that a man with an X-linked affected gene cannot pass it to his sons but would pass it to each daughter.

Kidney Research UK says that standard blood and urine tests check kidney function and look for blood and protein in the urine, and that genetic testing, which looks at a sample of your DNA, is the best way to diagnose Alport syndrome. About 3,000 different Alport gene variants have been identified, and some families have a unique variant. A kidney biopsy may also be required if signs and symptoms are not typical. Doctors also check for high-tone deafness and eye signs and ask about family history.

The NKF describes diagnosis by evidence of blood or protein leak in the urine along with hearing loss or a family history, by kidney biopsy, which shows a distinctive splitting of the filtering membrane, or by DNA testing. It says if someone has a known family history and blood in the urine, it is usually not necessary to perform a kidney biopsy.

Kidney Research UK says there is no cure, that treatments aim to slow progression and ease symptoms, and that ACE inhibitors can reduce protein loss. You may also be offered treatment for high blood pressure, anaemia or bone weakness, and be encouraged to eat a healthy diet, maintain a healthy weight, take regular exercise and avoid non-steroidal anti-inflammatory drugs. It says women with X-linked Alport syndrome, although less severely affected, should also be checked regularly and take the same precautions.

The NKF says high blood pressure is the most important factor that can speed up the decline in kidney function, and that strict control can delay the need for dialysis by years in some cases. It also advises that someone with Alport syndrome should have their ears and eyes tested to detect problems.

The NKF adds that there is some evidence high blood pressure can start in childhood, so starting treatment for high blood pressure even before the age of 10 can be beneficial. Treatment for high blood pressure consists of a healthy, salt-free diet with exercise, losing any excess weight, stopping smoking and limiting alcohol, and sometimes medicines.

The NKF says nearly all men and about 1 in 10 women with Alport syndrome develop kidney failure, that kidney failure develops slowly over years so that dialysis can be planned, and that most men develop kidney failure between 15 and 30, although in some families this is delayed to 50 to 70. It says nearly all people with Alport syndrome and kidney failure can have a kidney transplant if they are generally fit.

Kidney Research UK says that after a kidney transplant, Alport kidney problems do not recur in the transplanted kidney, although the transplanted kidney can sometimes be damaged by antibodies attacking normal collagen. The NKF describes a small risk of rejection due to anti-GBM disease after transplant that can be predicted by genetic testing but not completely avoided.

The NKF says relatives of someone with Alport syndrome can often be screened by a simple urine dipstick for blood, because people with the condition have small amounts of blood in the urine from a very early age. A negative test may need repeating several times, and blood can be present for other reasons such as a urine infection. It also advises that specialist advice is necessary given the complex inheritance, and that a kidney specialist and a genetic specialist can explain testing in more detail.

Kidney Research UK says individuals with affected Alport genes, for both X-linked and recessive inheritance, can pass these on to their biological children, and the chance of inheritance depends on which gene is affected. The NKF explains that a man with an X-linked affected gene cannot pass it to his sons but would pass it to each daughter, while a woman with Alport syndrome can pass it on to her children, including with severe disease to her sons.

The NKF says that where the gene change is known in a family, testing is possible, and that pre-implantation genetic diagnosis can be used on embryos created by IVF so that a child without Alport syndrome can be guaranteed. It advises consulting a kidney specialist and a genetic specialist for up-to-date information.

Kidney Research UK says that if you have been diagnosed with Alport syndrome, your kidney specialist or the nurse specialist at the kidney unit can answer questions, and it names Alport UK as a patient-led organisation that provides support and information. The NKF also runs a helpline.

Alport syndrome is usually diagnosed and followed through NHS kidney (renal) services, often with genetics input, after investigation of blood in the urine or a family history. Kidney Research UK says your kidney specialist or the nurse specialist at the kidney unit can answer questions about your care.

Some people seek a private nephrology opinion or genetic testing. If you do, ask for the results to be shared with your NHS kidney team and GP so your monitoring and family screening stay in one place.