Alport syndrome (Alport's syndrome)

from EdREN, the website of the Renal Unit of the Royal Infirmary of Edinburgh


What happens in Alport syndrome?
What trouble does Alport syndrome cause?
How is it inherited?
How can family members tell whether they have Alport syndrome?
Can it be cured?
What if kidney failure develops?
Where can I get further information?
Key points

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

 

What happens in Alport syndrome?

In each of the one million tiny filtering units (glomeruli) in each kidney, blood is filtered across the glomerular basement membrane (GBM). In Alport 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 (see pictures).

 

Normal

Alport
A very highly enlarged view of the filter in the glomerulus. These electron microscope images are magnified x100,000, and show glomerular basement membrane (G) in a normal glomerulus (LEFT) and in Alport syndrome (RIGHT). The diagrams below illustrate the thickening and 'falling apart' of Alport GBM.

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 syndrome cause?

Kidneys Most people with Alport syndrome develop kidney failure in early adult life - in their late teens or twenties. 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, at first to high tones, develops at round about the same age as kidney failure in most patients, although some people don't get this.

Eyes Harmless changes can quite often be seen at the back of the eye using special tests. Some patients have lenticonus, an unusual deformity of the lens of the eye.

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How is it inherited?

Alport 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 as high as 1 in 5, but most never get severe trouble, and those who do are usually much older than men who are affected.

In other families the gene involved (COL4A3 and COL4A4) is on another chromosome. In this case, men and women are equally affected, but otherwise the disease seems the same.

 

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How is the diagnosis made in the patient and their family?

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 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 a test which can only be done in some centres.

Other diseases can cause kidney trouble that runs in families, sometimes even with deafness.

 

Can I have genetic testing?

There is no simple blood test for Alport syndrome. Trying to find the problem in the gene is very difficult, and it is not likely that a simple test will become available in the near future. Precise genetic testing is possible in a few families, where the problem has already been sorted out.

In families with definite X-linked Alport Syndrome, it may be possible to do genetic tests to track the X chromosomes, and this can be helpful.


Can it be cured?

No. Complications of kidney failure can be prevented (see chronic renal failure and its progression), but the underlying problem cannot yet be cured. Many diseases with proteinuria are helped by treatment with ACE inhibitors (see blood pressure in kidney disease), and this type of treatment is likely to be suggested for most patients with protein in their urine.

Very interesting developments in research are now suggesting that bone marrow transplantation could help Alport syndrome, and it is likely that there will be new developments over the next few years.


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What if kidney failure develops?

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

Very occasionally (in less than 1 in 20 Alport transplants) kidney transplants meet with a unique problem. Because the transplanted kidney has normal type IV collagen, the immune system may see it as 'foreign' and attack it. This causes Alport anti-GBM disease, which is very similar to the kidney disease seen in Goodpasture's disease. Unfortunately it usually destroys the transplant.

 

Where can I get further information?

There are a number of resources on the web now. Here are a few:
The following EdRenINFO pages contain relevant information:

SMALL PRINT

Our page on disorders that may be confused with Alport Syndrome is for doctors and others with genetic and renal expertise.
Do you know other sources that should be included? Let us know

 

This information is published from the Renal Unit at the Royal Infirmary of Edinburgh, Scotland, UK, Renal@ed.ac.uk The author of this page was Neil Turner. It was first published in October 2000 and last updated Sunday, August 5, 2007.

Please be aware that while we have made all efforts to ensure that this information is accurate, we cannot guarantee that there are no mistakes. Also that the best management for individual patients may differ from that outlined here. Only the doctors caring for the patient will be able to advise on this.


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