J Korean Neurol Assoc.  1999 Sep;17(5):730-734.

A Novel Mutation in Exon 6 in a Patient with Fabry's Disease

• Kim JH
• Lee JK
• Yim SB
• Khang SK
• Kim KK

Abstract

Fabry's disease, angiokeratoma corporis diffusum, is a rare X-linked inborn error of glycosphingolipid metabolism due to the lack of the lysosomal enzyme, alpha-galactosidase A, resulting in a progressive intracellular deposition of neutral glycosphingolipids in various tissues, including the dorsal root ganglia, autonomic nervous system, vascular endothelial, and smooth muscle cells. Clinical manifestations of Fabry's disease result predominantly from the progressive deposition of globotriaocylceramide in the nervous system or vascular endothelium, and are characterized by acro-paresthesia, angiokeratoma, corneal opacity, TIA or stroke, ischemic heart disease, and renal failure. We report a case of a 19-year-old man presenting with a 12-year history of severe distal pain, acroparesthesia, short stature, and delayed puberty. An enzymatic assay disclosed substantially diminished alpha-galactosidase A activity and an electron microscopy of the peripheral nerve showed lipid inclusions which were composed of concentrically laminated, ovoid osmiophilic bodies in the perineural fibroblast and endothelial cells. These findings are typical of Fabry's disease and additional genetic study revealed deletion mutation(TTAG) at the 6th exon of the alpha-galactosidase A gene, which is a novel mutation that had never been reported in literatures. Symptomatic treatment with carbamazepine and clonazepam was tried with a good response.

Keyword

Fabry's disease; alpha-galactosidase A; Acroparesthesia

MeSH Terms

alpha-Galactosidase
Angiokeratoma
Autonomic Nervous System
Carbamazepine
Clonazepam
Corneal Opacity
Endothelial Cells
Endothelium, Vascular
Enzyme Assays
Exons*
Fabry Disease*
Fibroblasts
Ganglia, Spinal
Humans
Metabolism
Microscopy, Electron
Myocardial Ischemia
Myocytes, Smooth Muscle
Nervous System
Neutral Glycosphingolipids
Peripheral Nerves
Puberty, Delayed
Renal Insufficiency
Stroke
Young Adult
Carbamazepine
Clonazepam
Neutral Glycosphingolipids
alpha-Galactosidase