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 sonís 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)
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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