An atypical variant of Fabry's disease in men with left ventricular hypertrophy

N Engl J Med. 1995 Aug 3;333(5):288-93. doi: 10.1056/NEJM199508033330504.


Background: Fabry's disease is considered very rare. Left ventricular hypertrophy is one of the common manifestations in adults with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy.

Methods: We measured plasma alpha-galactosidase activity in 230 consecutive male patients with left ventricular hypertrophy. Clinical manifestations were assessed, endomyocardial biopsies were performed, and the patients were screened for mutations in the alpha-galactosidase gene.

Results: Seven of the 230 patients with left ventricular hypertrophy (3 percent) had low plasma alpha-galactosidase activity (0.4 to 1.2 nmol per hour per milliliter; 4 to 14 percent of the mean value in normal controls). These seven unrelated patients, ranging in age from 55 to 72 years, did not have angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities, which are typical manifestations of Fabry's disease. Endomyocardial biopsy was performed in five patients and revealed marked sarcoplasmic vacuolization in all five. Samples from four patients were examined by electron microscopy and revealed typical lysosomal inclusions with a concentric lamellar configuration in all four. Two patients had novel missense mutations in exon 1 (Ala20Pro) and exon 6 (Met296lle). The remaining five had no mutations in the coding region of the alpha-galactosidase gene, but the amounts of the alpha-galactosidase messenger RNA were markedly lower than normal.

Conclusions: Seven unrelated patients with atypical variants of hemizygous Fabry's disease were found among 230 men with left ventricular hypertrophy (3 percent). Fabry's disease should be considered as a cause of unexplained left ventricular hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • DNA / genetics
  • Diagnosis, Differential
  • Fabry Disease / complications*
  • Fabry Disease / enzymology
  • Fabry Disease / genetics
  • Fabry Disease / pathology
  • Humans
  • Hypertrophy, Left Ventricular / enzymology
  • Hypertrophy, Left Ventricular / etiology*
  • Hypertrophy, Left Ventricular / pathology
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Myocardium / pathology
  • RNA, Messenger / analysis
  • alpha-Galactosidase / blood
  • alpha-Galactosidase / genetics*


  • RNA, Messenger
  • DNA
  • alpha-Galactosidase