Fabry disease

Abstract

Previous reports of extensive lipid accumulation within neurons of the autonomic nervous system in Fabry disease suggest an anatomicopathologic basis for the peculiar pain, diminished sweating, and gastrointestinal symptoms experienced in this disorder. To further assess autonomic function in Fabry disease, noninvasive clinical tests were performed on 10 patients. Diminished sweating was found in each; the loss was approximately uniform proximally and distally, suggesting sweat gland dysfunction rather than autonomic neuropathy. Impaired pupillary constriction with pilocarpine, and reduced saliva and tear formation were found in half the patients. Disordered intestinal mobility was demonstrated in the oldest patients. In all cases, the cutaneous flare response to scratch and intradermal histamine was diminished, and pruritus was not experienced. Signs of autonomic dysfunction are present in Fabry disease and correlate with the known lipid deposition in autonomic neurons.

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

“…1 In affected individuals, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells and organs, where it participates by a yet unknown mechanism in the pathologies that are characteristic of Fabry disease. 1 Disease manifestations include acroparasthesias and neuropathic pain crises [2][3][4] ; angiokeratomas; cardiac involvement, including left-ventricular hypertrophy (LVH), valvular changes, ischemia, and myocardial infarction 5 ; cerebrovascular abnormalities resulting in stroke 6,7 ; autonomic nervous system dysfunction causing decreased sweat function 8 and reduced heart-rate variability 9,10 ; and kidney dysfunction progressing to end-stage renal disease (ESRD). 11 Fabry disease occurs in people of all ethnicities with an estimated incidence of about 1 in 117,000 male births, 12 although newborn screening studies have suggested a much higher incidence.…”

Fabry Disease: A Metabolic Proteinuric Nephropathy

“…Symptoms include episodes of extremity pain or acroparesthesia, gastrointestinal symptoms, hypohidrosis and associated heat sensitivity (Cable et al, 1982;Ries et al, 2005;Rowe et al, 1974) (Table 1). Pain has been linked with small fiber neuropathy (Attal & Bouhassira, 1999) and is thought t o b e c a u s e d b y e i t h e r r e d u c e d p e r f u s i o n o f p e r i p h e r a l n e r v e s o r g l y c o s p h i n g o l i p i d accumulation in neural or perineural cells (Gadoth & Sandbank, 1983;Gemignani et al, 1984).…”

Doença de Fabry

“…[29][30][31] Existem relatos de doentes com DF que apresentam hiperidrose, especialmente palmoplantar, que parece ser mais comum do que previamente acreditado, e mais prevalente nas mulheres. 16,[32][33][34] O pelo corporal pode ser acometido na DF na forma de hipotricose corporal difusa, pelo depósito direto de GL-3 nos folículos pilosos como também por alteração vascular de sua irrigação. 33 Outra alteração comumente detectável ao exame físico dermatológico é a presença de edema nas pálpebras e extremidades.…”