Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from south India

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.