Abstract
BACKGROUND: There is a paucity of literature from India on metachromatic leucodystrophy (MLD), a rare metabolic disorder of childhood resulting from aryl sulfatase A (ASA) deficiency.Patients/ METHODS: Case records of histopathologically verified cases of MLD, evaluated over a period of 12 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. RESULTS: The late infantile group (36) manifested with regression of milestones (all), delayed mile stones (14), gait abnormalities (14), and seizures (11). Despite spasticity (29), there was hypo/areflexia in 25 patients. Optic atrophy (six) was rare. Consanguinity was noted in 25 children and four had a history of similar illness in siblings. Behavioural problems dominated in the juvenile group (four), but associated cognitive decline and hyporeflexia provided a clue to the diagnosis. Low serum ASA (seven of 20), raised cerebrospinal fluid protein (five of 12), and urinary metachromatic granules (two of 32) were infrequent. Electrophysiological evidence of severe demyelinating and length dependent sensory motor neuropathy was observed in all, even in the presence of hyper-reflexia. In addition to metachromatic dysmyelinating neuropathy in all patients, sural nerve biopsy in 20 patients revealed orthochromatic deposits within perivascular macrophages, particularly among those patients with normal ASA values (11 of 14), suggesting the accumulation of other glycosphingolipids. CONCLUSIONS: This study produced some noteworthy observations: the high degree of consanguinity associated with MLD in India, the existence of MLD with normal serum concentrations of ASA, the deposition of orthochromatic lipids, and electrophysiological evidence of a partial conduction block.