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NORD is very grateful to Clifford Kashtan, MD, FASN, Director, Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School; Executive Director, Alport Syndrome Treatments and Outcomes Registry, for assistance in the preparation of this report.
Synonyms of Alport Syndrome
- Hematuria-Nephropathy Deafness
- Hemorrhagic familial nephritis
- Hereditary Deafness and Nephropathy
- Hereditary Nephritis
- Hereditary Nephritis With Sensory Deafness
- Autosomal Dominant Alport Syndrome (ADAS)
- Autosomal Recessive Alport Syndrome (ARAS)
- COL4A3-related nephropathy
- COL4A4-related nephropathy
- COL4A5-related nephropathy
- X-Linked Alport Syndrome (XLAS)
Alport syndrome is a rare genetic disorder characterized by progressive kidney disease and abnormalities of the ears and eyes. There are three genetic types. X-linked Alport syndrome (XLAS) is the most common; in these families affected males typically have more severe disease than affected females. In autosomal recessive Alport syndrome (ARAS) the severity of disease in affected males and females is similar. There is also an autosomal dominant form (ADAS) which affects males and females with equal severity. The hallmark of the disease is the appearance of blood in the urine (hematuria) early in life, with progressive decline in kidney function (kidney insufficiency) that ultimately results in kidney failure, especially in affected males. About 50% of untreated males with XLAS develop kidney failure by age 25, increasing to 90% by age 40 and nearly 100% by age 60. Females with XLAS usually do not develop kidney insufficiency until later in life. They may not develop kidney insufficiency or failure at all, but the risk increases as they grow older. Both males and females with ARAS develop kidney failure, often in the teen-age years or early adulthood. ADAS tends to be a slowly progressive disorder in which renal insufficiency does not develop until well into adulthood. Individuals with Alport syndrome can also develop progressive hearing loss of varying severity and abnormalities of the eyes that usually do not result in impaired vision. XLAS is caused by mutations in the COL4A5 gene. ARAS is caused by mutations in both copies of either the COL4A3 or the COL4A4 gene. ADAS caused by mutations in one copy of the COL4A3 or COL4A4 gene. Alport syndrome is treated symptomatically and certain medications can potentially delay the progression of kidney disease and the onset of kidney failure. Ultimately, in many cases, a kidney transplant is required.
The disease we now know as Alport syndrome was first described in the British medical literature in the early years of the 20th century. In 1927 Dr. Cecil Alport published a paper describing the association of kidney disease and deafness in affected individuals. Many additional cases were described in the literature and the disorder was named after Dr. Alport in 1961. Alport syndrome is often discussed with a related disorder known as thin basement membrane nephropathy (TBMN). Many cases of TBMN are caused by different mutations in the same genes that cause the autosomal recessive and dominant forms of Alport syndrome. TBMN is characterized by persistent microscopic blood in the urine (hematuria) in a similar pattern as seen in individuals with Alport syndrome. However, unlike Alport syndrome, TBMN is rarely associated with symptoms outside of the kidney (extrarenal abnormalities) and additional kidney findings such as protein in the urine (proteinuria), high blood pressure (hypertension), kidney insufficiency, and kidney failure rarely develop. It is extremely important to distinguish these disorders from one another because TBMN is much more common and a much milder disorder. The spectrum of disease that includes TBMN and Alport syndrome is sometimes referred to as collagen IV-related nephropathies. For more information on TBMN see the Related Disorders section of this report.
Alport Syndrome Resources
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