What is Alport's Syndrome?

Alport’s Syndrome is the second most common inherited cause of kidney failure. It usually affects young men, but it can affect older people and women.

In each of the one million tiny filtering units (glomeruli) in each kidney, blood is filtered across the glomerular basement membrane (GBM). In Alport’s Syndrome, type IV collagen, one of the proteins that makes up the GBM, is absent or abnormal. Although the GBM looks normal in childhood, it deteriorates with time because it lacks the special type IV collagen that should be there. As well as in the kidney, this special basement membrane collagen can also be found in some other parts of the body - most importantly in the inner ear and in parts of the eye.

What trouble does Alport’s Syndrome cause?

Kidneys: Most people with Alport’s Syndrome develop kidney failure in early adult life - most commonly in their twenties or thirties. Some (particularly women) only get the disease in later life. Before kidney function deteriorates, there may be blood and protein in the urine, and high blood pressure may develop. Women may never get much more than these changes, but some of them go on to get kidney failure over decades.

Deafness: Deafness develops at round about the same time as kidney’s deteriorate in most patients, although some people don't get this.

Eyes: Harmless changes may be seen at the back of the eye using special tests. Some patients have lenticonus, an unusual deformity of the lens of the eye, but this is usually a late development.

How is it inherited?

Alport’s Syndrome is much more common in boys and men because the gene that usually causes it (called COL4A5) is on the X chromosome. Women have two X chromosomes (XX), so they usually have a normal copy as well as an abnormal copy of the gene. Men have only one X chromosome (XY), so if they have a problem with the COL4A5 gene, that is their only copy. Boys who inherit the disease in this way must inherit it from their mother (as the mother contributes the X chromosome and the father the Y).

Women who carry the disease on one of their X chromosomes may have minor kidney trouble, such as blood or protein in the urine, sometimes with high blood pressure, but occasionally get severe disease and develop kidney failure. The lifetime risk of severe kidney disease for women who carry Alport's may be 1 in 5 or higher, but most never get severe trouble, and those who do are usually much older than men who are affected.

Diagnosis

The diagnosis is usually made after kidney biopsy and from the eye and hearing changes. If someone in the family has been shown to have Alport’s Syndrome, it is not usually necessary for everyone to go through all the tests. Sometimes doing a special test that involves looking at a sample of skin under the microscope can help, but this is not an easy or fool proof test and it can only be done in some centres. Where the diagnosis isn't certain, or genetic tests could help, clinical geneticists may be able to provide additional advice and special tests, including advice about ways to be sure that you don't pass on Alport’s Syndrome to another generation.

People with Alport’s syndrome are usually otherwise healthy and do very well on dialysis, and even better after a successful kidney transplant.

What is Alport's Syndrome?