Later-Onset Fabry Disease

Christopher S. Nance, Christopher J. Klein, Maryam Banikazemi, Steven H. Dikman, Robert G. Phelps, Justin C. McArthur, Moses Rodriguez, Robert J. Desnick
2006 Archives of Neurology  
Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of ␣-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. Lateronset variants with residual ␣-galactosidase A activity lack vascular
more » ... ndothelial 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 smallfiber 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,andmolecularstudieswereperformed. Results: Clinical evaluation suggested the diagnosis of Fabry disease, which was confirmed by reduced plasma and leukocyte ␣-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.
doi:10.1001/archneur.63.3.453 pmid:16533976 fatcat:cllkkzakhfbznmtprvi35a74iy