Alport syndrome Diagnosis

Early and accurate diagnosis is important for early intervention in Alport syndrome, regardless of gender.

“It is just as important to diagnose Alport syndrome in girls as in boys,” according to Dr. Clifford Kashtan. “Alport families know that affected boys will someday develop kidney failure, but they often believe that affected girls have no risk of kidney failure. Women with Alport syndrome may think that they are only carriers of a mutation and have no need for regular monitoring. The fact is that over 95% of women with Alport syndrome have blood in the urine, so they have the disease. Although the risk of kidney failure is much lower in women with Alport syndrome compared to men, there is a significant risk. About 20-30% of women with the X-linked form of Alport syndrome reach end-stage kidney disease by the age of 60. Women with Alport syndrome can also develop deafness.”

The diagnosis of Alport syndrome is performed using some or all of these methods:

  • Medical history and physical examination (urinalysis, blood testing)
  • Detailed family history and possibly urinalyses on first- and second-degree relatives
  • Hearing and vision evaluation and testing
  • Renal (kidney) ultrasound
  • Kidney biopsy analysis
  • Skin biopsy analysis
  • Genetic testing.
This diagram illustrates the missing Col4a5 tissue (green) in a biopsy sample. Left is normal, right is an X-linked Alport kidney. (Cosmo Bio Company, LTD.)

This diagram illustrates the missing Col4a5 tissue (green) in a biopsy sample. Left is normal, right is an X-linked Alport kidney. (Cosmo Bio Company, LTD.)

Kidney Biopsy

Alport syndrome produces unique changes in the walls of the blood vessels of the glomeruli (kidney structures) that can be detected by performing electron microscopy on the kidney biopsy material. A kidney biopsy is usually performed as an outpatient procedure at a hospital and requires minor surgery to obtain a sample of kidney tissue. Kidney biopsies can also be tested for the presence or absence of the type IV collagen alpha-3, alpha-4 and alpha-5 chains (COL4A3, COL4A4, and COL4A5 genes). This information is helpful in confirming a suspected diagnosis of Alport syndrome and can usually determine the genetic form of the disease.

See Diagnostic Labs for a listing of labs that perform analysis of kidney biopsies for Alport syndrome.

Skin Biopsy

A skin biopsy can be performed when XLAS (X-linked Alport syndrome) is suspected. The type IV collagen alpha-5 chain (COL4A5) is normally present in the skin and a biopsy of the skin can be tested for the presence or absence of this collagen chain. Approximately 80% of male patients and 60% of female patients with X-linked Alport syndrome will show abnormal staining for COL4A5 in the skin biopsy. This approach is especially useful if a kidney biopsy poses an excessive risk, such as in patients with kidney failure.

Because, the alpha-3 and alpha-4 chains are not present in the skin this test cannot be used to diagnose ARAS or ADAS.

See Diagnostic Labs for a listing of labs that perform analysis of skin biopsies for Alport syndrome.

Genetic Testing

Clinicians in many but not all parts of the world now have access to genetic testing for diagnosis of Alport syndrome through commercial laboratories or laboratories associated with medical institutions. Such testing offers high rates of diagnostic accuracy, particularly for X-linked Alport syndrome, although testing is available for autosomal recessive and autosomal dominant forms of the disease, too. Insurance coverage for genetic testing varies widely so patients are encouraged to seek the help of certified genetic counselors to determine their eligibility.

In most cases, genetic testing can confirm a diagnosis of Alport syndrome. Genetic testing is the only way to diagnose a female with no symptoms but with a family history of X-linked Alport syndrome.  Genetic testing may also be useful when results of a skin or kidney biopsy are not conclusive.

In cases where a parent has a known genetic mutation, prenatal diagnosis or pre-implantation genetic diagnosis (PGD) may be options. Prenatal diagnosis is possible through chorionic villi sampling (CVS) or amniocentesis. During CVS, fetal tissue samples are removed and enzyme tests are performed on cultured tissue cells and/or white blood cells. During amniocentesis, a sample of the fluid that surrounds the developing fetus is removed and studied. PGD can be performed on embryos created through in vitro fertilization. PGD refers to testing an embryo to determine whether it has the same genetic abnormality as the parent. Families interested in such an option should seek the counsel of a certified genetics professional.

See Genetic Testing Labs for a listing of labs that perform testing for X-linked, autosomal recessive and autosomal dominant forms of Alport syndrome.


References that were used to compile this discussion include: Clifford E. Kashtan, MD – Alport syndrome and Thin Basement Membrane Nephropathy; Alport syndrome Treatments and Outcomes Registry (ASTOR); National Organization of Rare Diseases, Alport syndrome
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