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Fabry disease: Neurologic manifestations

Raphael Schiffmann, MD, MHSc
Section Editors
Marc C Patterson, MD, FRACP
Scott E Kasner, MD
Deputy Editor
John F Dashe, MD, PhD


Fabry disease (also called angiokeratoma corporis diffusum, ceramide trihexosidosis, and Anderson-Fabry disease) is an X-linked glycolipid storage disease. It is caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, which causes progressive accumulation of α-D-galactosyl moieties, such as globotriaosylceramide (the glycolipid substrate for alpha-galactosidase A), within multiple cell types and tissues of affected patients [1,2]. Numerous mutations have been found in the alpha-galactosidase A gene (GLA gene) on the long arm of the X chromosome (Xq22) [3-5].

Clinical manifestations usually become evident by 10 years of age. Initial manifestations typically include neuropathy and characteristic skin lesions known as angiokeratomas. As patients age, cardiovascular and renal disease become increasingly prominent [6]. An overview of the clinical manifestations of Fabry disease and other related disorders is presented in the Table (table 1).

Progressive accumulation of globotriaosylceramide within endothelial, perithelial, and smooth muscle cells of the vascular system, dorsal root ganglia, and cells of the autonomic nervous system, result in the neurologic manifestations of the disease [2]. These include a small-fiber peripheral neuropathy and an increased propensity for ischemic stroke in affected males and female heterozygotes.

This topic will review the neurologic manifestations of Fabry disease and their treatment.

Other clinical aspects of Fabry disease are presented elsewhere. (See "Clinical features and diagnosis of Fabry disease" and "Fabry disease: Treatment" and "Fabry disease: Clinical features, diagnosis, and management of cardiac disease".)

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Literature review current through: Nov 2017. | This topic last updated: Jul 24, 2016.
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