The neurological manifestations of Fabry disease. A review

Abstract

Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Females may be severely affected as males and both may die prematurely due to stroke, heart disease and renal failure. Early recognition of symptoms, enzyme activity levels, concentration of Gb3 levels in the blood, urine and skin biopsies, as well as genetic testing (GLA gene) enable establishment of early diagnosis and therapeutic intervention with enzyme replacement therapy. Enzyme replacement therapy can stabilize or reduce the progression of the disease. Early therapy may prevent complications of the disease.