A novel mutation in the arylsulfatase A gene associated with adult-onset metachromatic leukodystrophy without clinical evidence of neuropathy.

! 45 and 47, respectively. His parents were not consanguineous and there is no previous history of similar neurological diseases in the family. Examination of the optic fundi showed no abnormal findings. He had no numbness, paresthesia, muscle weakness, muscle atrophy, abnormal involuntary movements or ataxia. Superficial sensation was normal, but vibratory sense was very slightly impaired in the lower limbs. The deep tendon reflexes were normal in the upper limbs. The patellar tendon reflexes were bilaterally increased, and the bilateral Achilles tendon reflexes were mildly diminished. The plantar responses were bilaterally extensor, but no spasticity was observed. Brain MRI revealed severe symmetrical white matter hyperintensities in the periventricular area on T2-weighted images and cerebral atrophy. Results from nerve conduction studies Dear Sir, Metachromatic leukodystrophy (MLD, MIM 250100) is an autosomal recessive hereditary disease characterized by neurological symptoms such as cognitive and behavioral abnormalities, ataxia and seizures [1] . MLD results from deficiency of arylsulfatase A (ASA), resulting in sulfatide accumulation in the central and peripheral nervous system [1] . A number of mutations in the ASA gene associated with decreased activity of ASA have been reported in patients with MLD [1] . Here we report a male patient with adult-onset MLD who is compound heterozygous for a novel nonsense mutation (C38X) (TGC ] TGA) and a known missense mutation (T409I) (ACT ] ATT) [2, 3] . Of note, this patient showed severely decreased nerve conduction velocities without obvious external clinical signs of neuropathy, normally a characteristic feature of MLD. The absence of clear external signs contributed to initial misdiagnosis. The 33-year-old male developed irritability and disorientation and visited a hospital department of psychiatry. There he was diagnosed with schizophrenia and, although he continued to take medications Received: November 21, 2007 Accepted: January 28, 2008 Published online: October 3, 2008