Advances in the management of Anderson-Fabry disease: enzyme replacement therapy

Anderson-Fabry disease (AFD) is a lysosomal storage disorder (LSD) due to alpha-galactosidase A (alpha-Gal A) deficiency and the resultant accumulation of incompletely metabolised glycosphingolipids (GSLs), primarily globotriosylceramide (Gb(3)), within various tissues. It is an X-linked multisystem disorder characterised by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement, and associated with significant impact on quality of life and diminished lifespan. The disease manifests primarily in hemizygous males; however, there is increasing recognition that heterozygous (carrier) females may also develop disease-related complications, although onset among affected women may be delayed. Until recently, treatment has been limited to symptomatic management of pain and other measures to alleviate the problems associated with end-stage complications from renal, cardiac and nervous system involvement. The availability of the recombinant enzyme offers the potential of a safe and effective targeted treatment approach. At the moment, two distinct enzyme formulations are approved in Europe (and in other countries) and both continue to undergo FDA evaluation in the US. Increasing knowledge of the natural history of AFD and greater experience with enzyme therapy should enable optimal patient care. The relative rarity and complexity of AFD necessitates a multi-disciplinary team approach that may be facilitated by a centralised registry.