Long-Term Effects of Enzyme Replacement Therapy for Anderson-Fabry Disease

Abstract

Anderson-Fabry disease is a rare X-linked lysosomal storage disease caused by α-galactosidase A (α-GalA) gene variants and characterized by a large genotypic and phenotypic spectrum. Enzyme replacement therapy (ERT) using recombinant α-GalA has been approved for > 10 years as a specific therapy for the disease. However, the long-term clinical efficacy for cardiac manifestations has been equivocal because it depends on several factors such as genotype, sex, age, and disease severity at the initiation of ERT. We report the differences in the clinical effects of ERT continued for > 10 years in three patients with the same genotype. Left ventricular hypertrophy and myocardial dysfunction progressed in the heterozygote proband even under ERT, although disease progression was prevented in two sons of Case 1.

Autophagy modulation enhances enzyme replacement therapy response in Fabry disease

“…This disease is characterized by progressive accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in cells of many tissues [2]. First clinical manifestations appear during the childhood (neuropathy, skin lesions, cornea verticillata) then, in adulthood, multivisceral complications occur gradually (hypertrophic cardiomyopathy, renal failure and recurrent strokes) [19].…”