Juvenile/adult‐onset galactosialidosis with remarkable clinical variabilities in two Japanese siblings

Abstract

Galactosialidosis is caused by mutations in the cathepsin A (CTSA) gene. We clinically and genetically examined two Japanese siblings with juvenile/adult‐onset galactosialidosis. Case 1‐1: A 39‐year‐old man was diagnosed as having mental retardation and epilepsy at 6 years. His visual acuity was impaired when he was 31 years, ophthalmological examination found cherry‐red spots in both eyes. Neurological examination revealed cerebellar ataxia, limb weakness, and myoclonus. Cerebral MRI showed diffuse cerebro‐cerebellar atrophy. Case 1‐2: A 36‐year‐old man at examination complained of impaired visual acuity when he was 29 years, cherry‐red spots were found in both eyes. Neurological examination revealed only occasional myoclonus. Genetic analysis confirmed a homozygous mutation (IVS7DS, A‐G, +3) in the CTSA gene in both cases. This mutation is known to cause juvenile/adult‐onset galactosialidosis only found in Japanese. Remarkable clinical differences among sibling cases were rare and prompted to reassess our understanding of the pathogenesis of galactosialidosis.