Alport
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Alport syndrome is a genetic disorder that results in nephropathy and
deafness. It is inherited as an X-linked trait, although some families have
been described in which consanguinity suggests the possibility of an autosomal
recessive form. The X-linked form of the disorder results from mutations in the
gene for the alpha-5 chain of basement membrane collagen (COL4A5). Affected
males have hematuria beginning in childhood that progresses to renal
failure in adulthood. Some patients present with massive hematuria during an
intercurrent infection. Female carriers of the trait have less striking
urinary findings and rarely develop uremia. Other features of the disease in
males include bilateral sensorineural deafness, hypertension, cataracts, and
in some cases, thrombocytopenia.
In the family presented in the vignette, the history of Alport syndrome in the
maternal grandfather and mother is indicative of an X-linked form of the
disorder. Because the mother is a mutant gene carrier, she has a 50% risk in
each pregnancy of passing on the X chromosome that contains the mutation.
Therefore, her son’s risk of being affected is 50%. Affected males should be
monitored beginning in childhood both for renal disease and hearing loss.
Acroparesthesias occur in Fabry disease, which is an X-linked lysosomal
storage disease that results from a specific enzyme deficiency. Wilms tumor is
not a feature of Alport syndrome.
IgA nephropathy (Bergers Disease)
References:
Crawfurd MA. Alport’s syndrome. J Med Genet. 1988;25:623-627
Kashtan CE. Alport syndrome. An inherited disorder of
renal, ocular, and cochlear basement membranes. Medicine. 1999;78:338-360
Knebelmann B, Breillat C, Forestier L, et al. Spectrum of
mutations in the COL4A5 collagen gene in X-linked Alport syndrome. Am J Hum
Genet. 1996;59:1221-1232