Later-onset Fabry disease: an adult variant presenting with the cramp-fasciculation syndrome

Arch Neurol. 2006 Mar;63(3):453-7. doi: 10.1001/archneur.63.3.453.


Background: Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of alpha-galactosidase A, typically presents in early childhood with acroparesthesias, angiokeratomas, hypohidrosis, and corneal dystrophy. The neuropathic pain presumably results from glycosphingolipid accumulation in the vascular endothelium and in small-caliber nerve fibers, and is treatable by enzyme replacement therapy. Later-onset variants with residual alpha-galactosidase A activity lack vascular endothelial involvement and classic symptoms, which lead to the development of cardiac and/or renal disease after the fourth decade of life.

Objective: To expand the later-onset Fabry phenotype to include cramp-fasciculation syndrome without small-fiber neuropathy.

Methods: A 34-year-old man who presented with chronic exercise-induced pain, fasciculations, and cramps of the feet and legs, and his similarly affected mother, were evaluated. Clinical, biochemical, and molecular studies were performed.

Results: Clinical evaluation suggested the diagnosis of Fabry disease, which was confirmed by reduced plasma and leukocyte alpha-galactosidase A activities (8.8% and 13.4% of normal, respectively) due to a missense A143T mutation. His mother was heterozygous for the A143T mutation.

Conclusion: The presentation of cramps and fasciculations without apparent small-fiber neuropathy expands the phenotype of later-onset Fabry disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age of Onset
  • Fabry Disease / complications*
  • Fabry Disease / genetics
  • Fabry Disease / metabolism
  • Humans
  • Leukocytes / metabolism
  • Male
  • Microscopy, Electron, Transmission / methods
  • Mutation, Missense
  • Neuromuscular Diseases / etiology*
  • Neuromuscular Diseases / genetics
  • Neuromuscular Diseases / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Skin / ultrastructure
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / metabolism


  • alpha-Galactosidase