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What is Alport’s syndrome?

Alport’s syndrome is an inherited kidney disease. This means it is caused by a genetic mutation and runs in families. Men are more severely affected than women. It can lead to deafness as well as kidney failure.

Why it is called Alport’s syndrome?

Alport’s syndrome is named after Professor Arthur Cecil Alport, who recognised families with the syndrome in 1927. He was born in 1880 in South Africa, and graduated as a doctor in Edinburgh. First, he worked in Johannesburg (owning a small gold mine). After the First World War he moved to St Mary's Hospital, Paddington, London, where he was working when he described the syndrome of hereditary renal failure and deafness. Later he worked in Cairo, and died in 1959.

What causes Alport’s syndrome, and differences between men and women?

Alport’s syndrome is caused by an abnormality in collagen in the body. Collagen is a ‘building block’, giving shape and strength to parts of the body not supported by bone. Cells, tiny packages of tissue that work to make energy and do all the 'work' inside our bodies, have no strength themselves. If cells were not held together, the human body would be like a lump of jelly. Bones are important in giving the human body shape and rigidity, but even soft tissues need holding together. This is the job of collagen.

There are several types of collagen, each of which are found in different parts of the body. Type 4 collagen is important in the kidney, ears and, to a lesser extent, in the eye. It is this type of collagen which is abnormal in Alport’s syndrome, leading to kidney failure, deafness, and abnormalities of the eyes. This abnormality occurs because the genetic code, which tells the body how to make collagen, is abnormal. Every gene as a specific name and the gene most commonly affected in Alport’s syndrome is called the COL4A5 gene. Other genes include COL4A3 and COL4A4. In around 15% of patients with the diagnosis, the genetic mutation arose in them rather than been passed from a parent.

The type 4 collagen gene is found on the ‘X’ chromosome, which determines the sex of a person. The human body has 23 pairs of chromosomes, one set from each parent. Hence, there are 46 chromosomes in total. One pair determines whether a person is male or female. This pair is made up of ‘X’ and ‘Y’ chromosomes. If someone has 2 X chromosomes  ‘XX’, they are female. If someone has one X chromosome and one Y chromosome,  ‘XY’, they are male. The Y chromosome is smaller than the ‘X’ chromosome, and it so happens that the COL4A5 gene is missing from the ‘Y’ chromosome. Therefore, if a male has a defective COL4A5 gene, there is no normal copy to help produce normal type 4 collagen. A woman has two ‘X’ chromosomes, hence the normal gene on the second chromosome helps produce normal type 4 collagen. Therefore, women with Alport’s syndrome are able to produce more normal collagen than men, and usually have mild disease. However they can pass Alport’s syndrome with severe disease, such as kidney failure to their sons. This type of inheritance, which is called 'sex linked' is important when family screening is considered. 

How is Alport’s syndrome diagnosed?

Alport’s syndrome can be diagnosed in several ways.

·        Evidence of blood or protein leak in the urine along with, a history of hearing loss or Alport’s syndrome in the family.

·        A kidney biopsy (sample of kidney removed with a needle to look under a microscope). Alport’s syndrome has a particular appearance in the kidney when examined under the microscope.

·        Testing DNA for genetic abnormalities, eg. COL4A5 gene.

Family screening

An explanation of which family members should be screened is given later. If someone is to be screened because of a family history, it may only be necessary to check the urine for blood. This can be done by taking a small sample of urine and dipping into it on a small plastic stick. Alport’s syndrome causes small amounts of blood to appear in the urine from a very early age. This test is not completely foolproof - a negative urine test may need to be repeated several times to be sure there is no blood, and blood can be present for other reasons, such as a urine infection.

Kidney biopsy

Alport’s syndrome causes a unique appearance when the kidney is examined under the microscope. Due to abnormal collagen the membrane that filters blood to make urine is split into several layers. Splitting is generally seen in men and in some women. Sometimes the membrane may just be very thin, which can make it more difficult to diagnose Alport’s syndrome.

If someone with a known family history of Alport’s syndrome has blood in the urine, it is usually not necessary to perform a kidney biopsy. However, in some cases where the diagnosis is not proven, it may be necessary.

Genetic testing

The problem is that many different (well over 100) genetic abnormalities can cause Alport’s, and these differ from family to family. Genetic tests looking for a single genetic abnormality are relatively easy to perform. If it is possible to determine which genetic abnormality is present in a particular family, testing is possible.

Technology is available to perform genetic tests on human embryos in the laboratory (pre-implantation genetic diagnosis), so that the production of a child without Alport’s syndrome can be guaranteed. However, these techniques mean that the human egg has to be fertilised ‘in vitro’, in other words a ‘test tube baby’.

If you want to know more about genetic testing, you should consult a kidney specialist and a genetic specialist for up-to-date information.

Diagnosis if typical eye abnormalities are found

Sometimes Alport’s syndrome is diagnosed after an eye specialist has noticed the unusual eye problems that Alport’s can cause. Also, high tone deafness in someone with a family history of kidney trouble may alert a doctor to the possibility of Alport’s syndrome.

 

Is it the same as Thin Basement Membrane disease?

You may come across the term ‘Thin basement membrane disease’ which some may consider as a milder version of Alport’s syndrome. This is caused by mild mutations in the gene coding for Type 4 collagen, causing thinning of the filter membrane in the kidneys. Hence the affected individuals commonly have near non-visible amount of blood in the urine, almost never have kidney disease and do not have abnormalities of the ears or eyes.  

Is Alport’s syndrome common?

Alport’s syndrome is not common. One or two out of 100 people starting dialysis have Alport’s syndrome, with a frequency in the general population of about 1 in 5,000, to 1 in 10,000. However, a greater number of women are likely to be carrying the mutated gene without symptoms.

Is there any treatment to prevent kidney failure in Alport’s syndrome?

At present, the abnormal gene cannot be replaced with a normal one hence no cure for Alport’s syndrome. However, as in all types of kidney disease, much can be done to try and reduce the rate of kidney damage, and to make someone feel as normal as possible as kidney failure develops.

High blood pressure is the most important factor that can speed up the decline in kidney function. Damaged kidneys cause high blood pressure, because one of the jobs of the kidneys is to control the level of blood pressure. High blood pressure damages the kidneys further, and so a vicious cycle develops. Strict control of the blood pressure can break this cycle, delaying the need for dialysis by years in some cases. There is some evidence that high blood pressure can start in childhood, so that 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. Any excess weight should be lost. Stop smoking and drink no alcohol, or have only a moderate intake. In most people with significant kidney disease, it is also necessary to use medications to reduce the blood pressure. Up to 4 or 5 different types of medications may be necessary in some people.

As kidney failure becomes advanced, anaemia may develop, which can be managed effectively with a drug called EPO.

What about ear and eye damage - is this serious?

Someone with Alport’s syndrome should also have their ears and eyes tested to detect any problems.  

The inner ear contains type 4 collagen and is affected by Alport’s syndrome. Men are affected more than women. Some men may develop bilateral partial deafness, especially for high tones, and may require a hearing aid by the time they are in their late teens. However, this is not universal in Alport’s. Kidney failure may make the deafness worse, with some improvement after a kidney transplant. Women may have some hearing loss that could be detected by special tests done in hospital, but this does not often cause problems with normal conversation.

The medical term for the most common problem in the eye is ‘bilateral anterior lenticonus’ This means that, in both eyes, the front surface of the lens, the part of the eye over the pupil, bulges forwards. This change may be slight, and not visible to the naked eye. It may cause short sightedness, and it may be necessary to wear glasses. There may also be some dots and flecks on the back of the eye, but these are only visible to an eye specialist and should not affect vision.

Does everyone with Alport’s syndrome develop kidney failure?

Nearly all the men and about 1 in 10 women with Alport’s syndrome develop kidney failure. However, Alport’s syndrome can vary slightly from family to family. There is also a rare subtype of Alport’s in which kidney failure occurs in childhood.

It is rare for men with Alport’s to develop kidney failure before the age of 10 years. Most men develop kidney failure between the ages of 15 and 30, though in some families this is delayed to 50-70 years. Kidney failure develops slowly over a period of years, so that the need for dialysis can be planned; or in some cases, a kidney transplant might be carried out before dialysis was necessary.

Women with Alport’s syndrome have tiny amounts of blood in their urine (haematuria), sometimes with some protein. About 6 out of 10 women may develop protein in the urine. Although protein in the urine suggests a risk for progression to kidney failure, in many cases the kidney function remains normal and only about 1 in 10 women with Alport’s syndrome ever need dialysis or a kidney transplant.

Can people with Alport’s syndrome have dialysis or a kidney transplant?

Alport’s syndrome does not cause particular problems with dialysis. Nearly all people with Alport’s syndrome and kidney failure can have a kidney transplant, so long as they are generally fit. If a healthy family member is being considered as a donor they would have to undergo meticulous investigation. In general, kidney transplantation in Alport’s syndrome has a small risk of rejection due to Anti-Glomerular Basement Membrane Glomerulonephritis (Anti-GBM disease). This risk could be predicted by genetic testing of the recipient but no completed avoided.  

Should members of the family have tests to look for Alport’s syndrome?

Yes. Both men and women with Alport’s syndrome have small amounts of blood in the urine from a very early age, so it is easy to test for Alport’s syndrome in relatives of someone known to be affected. However, it is not necessary to test every single family member. Specialist advice is necessary given the complex genetic inheritance of the disease. The above description of the inheritance of Alport’s syndrome applies to the 9 out of 10 families who have the commoner genetic problem. Some families are more complicated, and advice should be taken from a specialist in genetics.

The need for testing family members will be discussed from the point of view of a man with Alport’s syndrome, and then from the point of view of a woman with Alport’s syndrome.

Who to test if a man has Alport’s syndrome

His parents

Alport’s syndrome should have been inherited from his mother, though occasionally the genetic abnormality has occurred for the first time in the affected person. His mother should have urine tests for blood. If there is blood in the urine, kidney function and blood pressure should be tested, and a kidney specialist consulted. If the mother is completely clear, the father should be checked, in case there is a rarer variant of Alport’s syndrome.

His brothers

There is a 50:50 chance that a brother will have Alport’s syndrome. Urine should be tested for blood. If he has blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. A brother might have Alport’s syndrome, and could pass this onto his daughters. If there is no blood in the urine on several tests, he should not have the Alport’s syndrome gene, and so cannot pass the condition onto his children.

His sisters

There is a 50/50 chance that each sister will have Alport’s syndrome, though remember that this is less serious in women than in men. Urine should be tested for blood. If she has blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. If she has Alport’s syndrome, she could pass this onto her children. If there is no blood in the urine on several tests, she should not have Alport’s syndrome, and so cannot pass the condition onto her children.

His sons

A man with Alport’s syndrome cannot pass the condition onto his sons (unless he has one of the rarer variants of the disease). This is because the abnormal gene is on the ‘X’ chromosome, and in order to have a son, a man has to pass on his ‘Y’ chromosome to the child, and this does not carry Alport’s syndrome.

His daughters

Each daughter will have Alport’s syndrome, though remember that this is less serious in women than in men. Urine should be tested for blood to confirm the diagnosis. Kidney function and blood pressure should be measured, and a kidney specialist consulted. She could pass Alport’s syndrome onto her children (see below).

Who to test if a woman has Alport’s syndrome

Her parents

Alport’s syndrome should have been inherited from her mother or father. Her parents should have urine tests for blood. If there is blood in the urine, kidney function and blood pressure should be tested, and a kidney specialist consulted.

Her brothers

If Alport’s syndrome is inherited from the father, the male children should not have the syndrome. If Alport’s is inherited from the mother’s side, there is a 50:50 chance that he will have Alport’s syndrome. Urine should be tested for blood. If there is blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. He might have Alport’s syndrome, and could pass this onto his daughters. If there is no blood in the urine on several tests, he should not have Alport’s syndrome, and so cannot pass the condition onto his children.

Her sisters

If Alport’s syndrome is inherited from the father, the female children should all have Alport’s syndrome. If Alport’s syndrome is inherited from the mother’s side, there is a 50:50 chance that the sister will have Alport’s syndrome. Urine should be tested for blood. If there is blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. She might have Alport’s syndrome, and could pass this onto her children. If there is no blood in the urine on several tests, she should not have Alport’s syndrome, and so cannot pass the condition onto her children.

Her sons

There is a 50:50 chance that each son would have Alport’s syndrome. Urine should be tested for blood. If there is blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. He might have Alport’s syndrome, and could pass this onto his daughters. If there is no blood in the urine on several tests, he should not have Alport’s syndrome, and so cannot pass the condition onto his children.

Her daughters

There is a 50:50 chance that a daughter will have Alport’s syndrome. Urine should be tested for blood. If there is blood in the urine, kidney function and blood pressure should be measured, and a kidney specialist consulted. She might have Alport’s syndrome, and could pass this onto her children. If there is no blood in the urine on several tests, she should not have Alport’s syndrome, and so cannot pass the condition onto her children.

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Last reviewed January 2024
Next review January 2027

Reviewed by Dr Oshini Shivakumar 'Specialist Renal Registrar'

The National Kidney Federation cannot accept responsibility for information provided. The above is for guidance only. Patients are advised to seek further information from their own doctor.