• Fabry disease
• carrier females

• α-Gal A, α-galactosidase A
• GL-3, globotriaosylceramide

We write in support of the article by MacDermot et al,¹ which described the clinical manifestations and impact 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 glycosphingolipids, predominantly globotriaosylceramide (GL-3), in the viscera and vascular endothelium throughout the body, causing 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, symptomatology 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 chromosome in some or all cells of the female embryo being randomly 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 …