Alport

  1. subtype of hereditary glomerulonephritis
  2. commonly present with asymptomatic microscopic hematuria, but recurrent episodes of gross hematuria are common
  3. progressive HTN and proteinuria occur early with gradual decline in renal function
  4. males commonly develop end-stage renal failure in the 2nd or 3rd decade of life; elicit family hx of endstage renal failure esp in young males
  5. may have sensorineural hearing loss
  6. 10% of patients have eye abnormalities (e.g., cataracts)
  7. X-linked dominant disorder, but autosomal transmission has been described
  8. in the X-linked form, the disease results from mutations in the gene that encodes the alpha-chain of type 4 collagen
  9. females less affected but can be carriers

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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 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)


References:
Crawfurd MA. Alportís 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