Alport Syndrome Diagnosis

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 ultrasound
  • Kidney biopsy analysis
  • Skin biopsy analysis
  • Genetic testing.

Kidney Biopsy

Alport Syndrome produces unique changes in the walls of the blood vessels of the glomeruli 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, COL4A5). This information is helpful in confirming a suspected diagnosis of Alport Syndrome and can usually determine the genetic form of the disease (XLAS, ARAS, or ADAS). 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. A skin biopsy is less invasive than a kidney biopsy and can be done in a doctor’s office so this should be considered first for diagnosis of suspected XLAS patients. 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

If diagnosis remains doubtful after kidney and/or skin biopsies, screening for genetic mutations may be considered. However, the screening for COL4A3, COL4A4, and COL4A5 is expensive, time consuming, extremely difficult and not widely available (see Genetic Labs). In addition, the current detection rate of COL4A5 mutations in relatives is only about 50%. Thus, for now, genetic analysis should be limited to prenatal diagnosis or when uncertainty about diagnosis or mode of inheritance of Alport Syndrome exists.

Thin Basement Membrane Nephropathy

In some people with hematuria (blood in the urine), it is difficult to determine whether they have Alport Syndrome or Thin Basement Membrane Nephropathy because these conditions can have a very similar appearance, especially in children. However, a kidney biopsy should be able to show normal results for type IV collagen chains (COL4A3, COL4A4, COL4A5) indicating a diagnosis of Thin Basement Membrane Nephropathy. This is an autosomal dominant disorder characterized by hematuria that rarely progresses to proteinuria and kidney failure.