Fabry disease in females

Abstract

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of alpha galactosidase A and accumulation of globotriaosyl ceramide (Gb3) in cells throughout the body. Despite X-linked inheritance, females with Fabry disease may manifest significant multi-system pathology with effects on organ function, physical symptoms, quality of life and survival. Lyonisation within the peripheral blood results in some females exhibiting normal plasma or leucocyte enzyme activities which can lead to difficulties in diagnosis. Evidence of Gb3 storage has been found in urine and plasma and by histological analysis of renal and cardiac biopsies. However the disease causing mechanisms, given the presence of some enzyme activity from the normal alpha galactosidase A gene are not clear. Therapeutic effects of alpha galactosidase A have been demonstrated in the clinical trials, registries and case studies of females with documented improvements in pain, quality of life, left ventricular cardiac mass, and stabilised renal function. The optimum timing for initiation of enzyme replacement therapy nor its role in pregnancy and lactation is unknown. There is a necessity to develop strategies to identify which females are most like to benefit from Fabry specific therapy. © 2010 Springer Science+Business Media B.V.