Japanese patients with Fabry disease predominantly showing cardiac and neurological manifestation with novel missense mutation: R220P

BackgroundFabry disease, an X-linked lysosomal sphingolipid storage disorder caused by mutation of the α-galactosidase A (GLA) gene, results in systemic organ damage. However, the age of onset of clinical manifestations and course of the disease are variable even within the same family.ObjectiveIn this study, we evaluated the clinical phenotype and the molecular lesions associated with the GLA gene in a Japanese family with Fabry disease that predominantly showed cardiac and neurological manifestations.MethodsA genetic analysis of the GLA gene using conventional genomic sequencing was performed in all seven members of this family, including four hemizygous males and three heterozygous females. Endomyocardial biopsy was performed in two patients with severe left ventricular (LV) hypertrophy.ResultsA novel missense mutation was identified at codon 220 in exon 5, thus resulting in an arginine to proline substitution (R220P) in all seven family members. The three adult hemizygous males had LV hypertrophy and developed neurological manifestations in their 50 s. One of the adult hemizygotes developed complete atrioventricular block. On the other hand, we could not find any organ damage in a young hemizygous male or the three heterozygous females.ConclusionWe identified a novel missense mutation in a Japanese family with Fabry disease showing cardiac and neurological manifestations. In patients with Fabry disease, advanced organ damage in the heart and brain can be life-threatening, even if renal failure is lacking.