[Two siblings with metachromatic leukodystrophy of adult and juvenile onset]

We reported two siblings with metachromatic leukodystrophy of adult and juvenile onset. Patient 1, a 24-year-old female had been unremarkable until 23 years, when she began to develop loss of spontaneity, bradykinesia and gait disturbance. Nine months later, she became unable to walk and mentally deteriorated. Neurological examination disclosed dementia, frontal signs and hyperreflexia. Patient 2, a 22-year-old male, brother of patient 1, whose fetal development and birth were uneventful, developed muscle weakness at 12 years old, had difficulty in walking and writing at 13, mental deterioration at 16 and became bedridden and presented with tonic-clonic seizures at 19. Neurological examination at 24 revealed dementia, frontal signs, hyperreflexia and ataxia. In both patients computed tomography scans displayed low density in the cerebral white matter, and the nerve conduction velocities were decreased. Arylsulfatase A activities in urine (33% of normal) and leukocytes (8% of normal) were markedly reduced. Molecular genetic analysis identified the mutation 426Pro --> Leu (allele 426) as has been reported in adult type metachromatic leukodystrophy in Germany. As far as we know, only one sibling with adult type or juvenile type metachromatic leukodystrophy has been reported in Japan. This is the first report of siblings with 426Pro --> Leu mutation in Japan.