How is Alport Syndrome Diagnosed?

There are various methods of identifying whether a patient has Alport syndrome. The syndrome presents in significant ways in some patients but with less obvious symptoms in other patients, and there are several ways of determining the condition in most affected people, as outlined below.

Genetic testing

Genetic testing provides a way of identifying all types of Alport syndrome. Although genetic testing for the condition can be difficult due to the large molecules involved, it can provide the patient with a probable diagnosis.

This method is particularly good for patients who are suspected of having X-linked Alport Syndrome, which accounts for about 80% of cases. Patients with the even rarer forms of autosomal recessive and autosomal dominant, also have options with this type of test. It can also be particularly useful for patients who have gone through other kinds of testing but have received fairly inconclusive results from those.

Some patients can be mainly carriers of the gene and have very few symptoms aside from possible hematuria. However, if they have a family history of X-linked Alport Syndrome, a diagnosis may be beneficial because of how it can affect descendents.

Genetic testing is one method that can be used to identify whether the child of a parent who has an Alport syndrome mutation also has the syndrome. This can be carried out while the child is developing in the womb.

Amniocentesis is a test used by medical staff to determine whether a developing baby has a genetic disease. Cells are extracted from the amniotic fluid around the womb of a pregnant woman using a long, thin needle. The process can take about 10 minutes. The mother usually goes through the procedure between the 15th and 20th week of pregnancy. However, there can be a 1 % risk of miscarriage due to the procedure.

Another test is chorionic villus sampling, where cells are extracted from the placenta linking the developing child’s blood supply to the mother’s. This can be performed between the 10th and 14th week of the pregnancy. This test also takes about 10 minutes to carry out.

Skin Biopsy

This is a useful method for A-linked alpha-5 Alport syndrome but cannot be used for alpha-3 or alpha-4. A small amount of skin tissue is taken and undergoes an immunostaining procedure.

Normal skin samples tend to have alpha-5 chains in them but these are rarely found in the skin samples of males with X-linked A5. An antibody that reacts with the collagen type IV alpha-5 chain is added to the skin cells and observed for a reaction. This test helps clinical staff to identify how much of the protein is present.

Kidney Biopsy

Electron microscopy is used to determine whether characteristic Alport syndrome changes have occurred to the walls of the glomeruli involved in the water and waste filtering process in the kidneys. A small sample of tissue from the kidney is examined to make that diagnosis.

In addition, immunostaining can also be used on kidney biopsy material. It can be tested to observe the presence and quantities of the alpha-3, alpha-4 and alpha-5 types.

Other contributing diagnostic methods

Aside from the clinical tests that help to diagnose specific types of Alport syndrome, patients will go through other processes.

Medical staff will discuss the patient’s medical history with them and also carry out physical examinations to see if there are any signs. They will also ask them about the medical history of their closest relatives to pick up further clues

A hearing test can be carried out as many patients with Alport syndrome are affected by hearing loss. Also the patient’s eyes will be examined to see if there are any changes to the shape of the eye lens as this can become conical with the syndrome.

References

• National Organization for Rare Disorders on Alport Syndrome diagnosis: http://rarediseases.org/rare-diseases/alport-syndrome/
• NHS Choices on amniocentesis: http://www.nhs.uk/Conditions/Amniocentesis/Pages/Introduction.aspx
• NHS Choices on chorionic villus sampling: http://www.nhs.uk/conditions/chorionic-villus-sampling/pages/introduction.aspx
• Journal of the American Society of Nephrology, Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy on Alport Syndrome diagnosis: http://jasn.asnjournals.org/content/24/3/364.full