ELECTRONIC LETTER Clinical presentation in female patients with Fabry disease

We write in support of the article by MacDermot etal,1 which described the clinical manifestations andimpact of disease in a cohort of 60 obligate carrier female patients with Fabry disease. Fabry disease is a lysosomal storage disorder resulting from a deficiency of the enzyme α-galactosidase A (α-Gal A). Deficient concentrations of the enzyme result in an accumulation of glycosphingolip-ids, predominantly globotriaosylceramide (GL-3), in the viscera and vascular endothelium throughout the body, caus-ing multiple manifestations. Fabry disease is considered to be an X linked recessive disorder, in which symptoms in carriers are expected to be rare and, if present, very mild. However, the article by MacDermot et al is one of several publications reporting that many heterozygous female patients display classical symptoms of Fabry disease.1–5 Overall, symptomatol-ogy is usually more severe in hemizygous male patients with Fabry disease, but disease expression can vary widely in both sexes. Some female carriers remain asymptomatic and have normal concentrations of α-Gal A, whereas some experience more severe manifestations of disease. This variability can be both between and within families and is thought to be partly the result of Lyonisation, a process that results in one X chro-mosome in some or all cells of the female embryo being ran-domly inactivated. Thus, female carriers are essentially a mosaic of normal and mutant cells in varying proportions.6 In view of this, a review of the medical records of 11 female patients with Fabry disease (derived from eight families) being monitored at the Edouard Herriot Hospital, Lyon was undertaken to evaluate the clinical range of their disease. METHODS Eleven patients were selected from all the female patients with Fabry disease currently being monitored in Lyon, on the basis that complete clinical and paraclinical data (including renal function (inulin clearance), cardiac, and ophthalmic investi-gations) were available for all 11 patients