LAUSR

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-gal A, leading to the progressive accumulation of sphingolipids. Enzyme replacement therapy (ERT) is the most common therapy at present which has been approved in Japan since 2004. Different degrees of clinical improvements by ERT were reported in numerous articles based on patients’ compliance, improved GFR, improved cardiac activity and etc. Few direct evidences of tissue biopsy during ERT were reported so far except for kidney biopsy. Here, we present plasma lyso-Gb3 data and electron microscopy (EM) of skin biopsy from 30 cases including male and female who are receiving ERT for almost 13 years. All the cases were diagnosed based on their family history, clinical, biochemical and molecular findings. Lyso-Gb3 was measured in plasma, skin biopsy was taken for electron microscopy (EM). The IgG antibody titer of the patients were measured against alpha-gal A enzyme. The male patients having severe type of mutations with high antibody titers showed high plasma lyso-Gb3 and still massive accumulation of sphingolipids in the fibroblasts, exocrine glands and Schwan cells. The severely affected female cases also showed high lyso-Gb3 and sphingolipids accumulation. Morphological pictures in treated female cases showed rather different patterns from those of male. The patients who were receiving ERT before the phenotype appeared, had low plasma lyso-Gb3 and minimal sphingolipids accumulations in skin by EM. Several reports suggested that high plasma antibody titer minimizes the effect of the enzyme and also the uptake of enzyme were varied by tissues or cell types. Our studies clearly indicate that EM studies in skin plus plasma lysoGb3 measurement could be valuable for the evaluation of the efficacy of ERT to follow up Fabry patients.