Alport syndrome

What is it?

Alport syndrome is the second most common inherited cause of kidney failure. There are many other, much more common, non-inherited causes of kidney failure, such as:

• Diabetes
• High blood pressure
• Glomerulonephritis (inflammation of the kidney that may develop for a variety of reasons)

It occurs when a special type of collagen (Type IV collagen) normally found in all tissues but especially in the kidney, inner ear and eyes, is missing or abnormal.

One of the early signs of Alport syndrome may be small amounts of blood or protein in the urine during childhood. This occurs from membranes in the kidneys filtering units, or glomeruli.

Blood loss is usually microscopic and so not visible, but may be greater if the child is unwell, for example if they have a viral illness. Then the urine may become pink, or smoky red, although this settles as the child recovers.

High blood pressure may develop. However kidney failure doesn’t usually develop until late teens or adulthood. At around the time that the kidneys start to fail, deafness, especially to high tones, may also become a problem in many of those affected but not all.

The surface of the front of the eye or cornea may become more vulnerable to damage, and the lens may be an unusual shape which causes a slowly progressive deterioration in sight. Changes at the back of the eye may also be seen during opticians tests but don’t usually cause problems.

Who's affected?

About one in 5,000 people are affected by Alport syndrome. Because of the way in which it's inherited, it's more common among males.

The gene that causes most cases (called COL4A5) is on the X chromosome. Women have two X chromosomes, so they usually have a healthy gene as well as the faulty one, but men don't have a healthy X chromosome because they have X and Y chromosomes. Women who carry the faulty gene may have minor kidney problems but sometimes may have more serious kidney disease, usually later in life.

However, Alport Syndrome can also be caused by a mutation of a different gene, which is not linked to the X chromosome but is on one of the other chromosomes and inherited in an autosomal dominant or an autosomal recessive fashion. In these cases girls are equally as likely as boys to develop problems.

In most cases there is a family history of the problem but 15 to 20 per cent of sufferers don't have a family history and it is caused by a new gene mutation.

How is it diagnosed?

The patient’s story and symptoms are often a strong clue to the diagnosis especially in a family known to be at risk. But diagnosis can be difficult because of similarities with other kidney diseases. A kidney biopsy may be carried out, usually as an outpatient procedure, or in some cases a skin biopsy may be done.

Genetic testing is more complicated as the abnormal genes are difficult to detect, although genetic testing may be possible in families where the problem has already been thoroughly studied.

What's the treatment?

Treatment consists of controlling high blood pressure and restricting salt, protein and phosphate in the diet. Eventually, dialysis and kidney transplant may be necessary.