Alport syndrome is a rare genetic mutation that gets passed down to about 1 in 50,000 infants. The Genetics Home Reference of the U.S. National Library of Medicine—which forms part of the National Institutes of Health—offers a primer on Alport syndrome’s symptoms, causes, and treatments.*

What are the symptoms of Alport syndrome?

People with Alport syndrome develop:

• progressive loss of kidney function, often resulting in end-stage renal disease (ESRD);
• sensorineural hearing loss (permanent hearing loss caused by damage to the inner ear or to the nerve from the ear to the brain);
• misshapen eye lenses (located behind the iris and pupil), discoloration of the retina, and other eye abnormalities, though these rarely lead to loss of vision;
• hypertension (high blood pressure); and
• edema (fluid retention and swelling) in the legs and ankles.

Symptoms related to vision and hearing tend to be more severe in males than in females.

What causes Alport syndrome?

Alport syndrome is caused by mutations in the COL4A3, COL4A4, and/or COL4A5 genes. These genes affect the production of a protein called Collagen IV. This type of collagen forms structural support membranes in the kidneys, cochlea (spiral cavity of the inner ear), and eyes. 

In your kidneys, these mutations impede the function of the glomeruli, tiny blood vessels that:

• filter your blood,
• remove wastes and excess water, and 
• generate urine. 

Alport syndrome can be inherited in three ways or patterns:

1. X-linked (XLAS): The mutated gene is located on the X chromosome, one of the two sex chromosomes (the other being the Y chromosome). Approximately 80% of cases are passed down this way, though fathers cannot pass X-linked traits to their sons.
2. Autosomal recessive (ARAS): Each parent carries one copy of the mutated gene on a non-sex chromosome. If both parents don’t have it, the disease won’t be passed down. Approximately 15% of cases are passed down this way. Not all carriers of the gene will exhibit symptoms.
3. Autosomal dominant (ADAS): Only one parent needs to carry the mutated gene on a non-sex chromosome in order to pass it down. Only about 5% of cases are passed down in this way. This form involves a mutation in either the COL4A3 or COL4A4 gene, not the COL4A5 gene. 

How is Alport syndrome diagnosed?

In addition to noticeable symptoms, such as gradual hearing loss, almost all people affected by Alport syndrome will have hematuria (blood in their urine) and proteinuria (high levels of protein in their urine, identified through blood and urine tests). Both of these conditions indicate abnormal kidney function. 

How is Alport syndrome treated?

Alport syndrome is treated in the same ways as other types of chronic kidney disease, with a focus on managing symptoms and slowing progression. 

Treatment methods generally include:

• lifestyle changes (including a low-salt diet, exercise, and quitting smoking);
• medications (mainly to control hypertension); and
• supplements, such as diuretics (pills to help flush excess fluids from your body).

There is currently no way to slow or reverse hearing loss from Alport syndrome, but most patients are good candidates for hearing aids. For those approaching kidney failure, dialysis and kidney transplantation are options to discuss with your healthcare provider. 

For further information, please visit the National Kidney Foundation page on Alport syndrome and the Renal Fellow Network’s topic discussion on “Mutations in Type IV Collagen and Their Clinical Significance in Kidney Disease.”

*Alport syndrome. (2020, July 7). Genetics Home Reference, U.S. National Library of Medicine, National Institutes of Health.