MLD

Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal storage disorder caused by deficient activity of the enzyme arylsulfatase A (ARSA), encoded by the ARSA gene. The deficiency leads to accumulation of sulfatides in lysosomes, particularly in oligodendrocytes and Schwann cells, resulting in progressive demyelination of the central and peripheral nervous systems.

MLD is inherited in an autosomal recessive manner. Onset ranges from infancy to adulthood and is categorized into late-infantile, juvenile, and adult forms, reflecting age at onset and disease trajectory. Early symptoms often include motor delay, hypotonia in infants, gait disturbances, and progressive ataxia, followed by cognitive decline, spasticity, and peripheral neuropathy. The disease features widespread white matter degeneration on MRI, with characteristic changes seen on T2-weighted images.

Diagnosis combines clinical presentation with biochemical and genetic tests. Reduced ARSA enzymatic activity in leukocytes or fibroblasts confirms suspicion, supported by molecular testing identifying biallelic ARSA mutations. Elevated sulfatide levels in urine and characteristic neuroimaging findings aid assessment.

There is no cure. Management is multidisciplinary and supportive, focusing on maintaining mobility, communication, nutrition, and reducing complications. Some patients may benefit from hematopoietic stem cell transplantation when performed early in the disease course, though results are variable. Research into disease-modifying approaches, including gene therapy and enzyme replacement strategies, is ongoing.

Epidemiology: MLD is a rare disorder, with an estimated incidence ranging roughly from 1 in 40,000 to 1 in 160,000 births, varying by population. The term metachromatic refers to the staining properties of accumulated sulfatides with certain dyes.