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

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.