Newborn screening for Fabry disease in Japan: prevalence and genotypes of Fabry disease in a pilot study. Newborn screening for Fabry disease in the western region of Japan. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Epidemiology of lysosomal storage diseases: an overview, in Fabry Disease: perspectives from 5 Years of FOS. : database of the clinical phenotypes genotypes and mutant ⍺-galactosidase A sturctures in Fabry disease. Fabry disease, an under-recognized multisystemic disorder:expert recommendations for diagnosis, management, and enzyme replacement therapy. Fabry disease: a review of current management strategies. We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%). Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. Fabry Stabilization Index was used to determine the clinical severity. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. In all cases, heterozygous pathogenic variants in the GLA gene were detected. We present five female patients from one family and four individual female patients with Fabry disease. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. Previous studies examined this correlation using the classical methylation-dependent method however, conflicting results were obtained. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Males are usually severely affected, while females have a wide range of disease severity. Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A.