leukodystrofi

Leukodystrophy refers to a group of inherited disorders characterized by abnormal development or degeneration of myelin, the fatty sheath that insulates nerve fibers in the brain and spinal cord. These conditions arise from genetic defects that disrupt formation, maintenance, or turnover of white matter.

Most leukodystrophies are caused by mutations affecting enzymes, transporters, or structural proteins involved in myelin metabolism. Inheritance patterns are diverse, including autosomal recessive, X-linked, and, less commonly, autosomal dominant. Common forms include metachromatic leukodystrophy, Krabbe disease, and X-linked adrenoleukodystrophy.

Clinical presentation varies by subtype and age of onset, from early infancy to adulthood. Symptoms typically include motor impairment (paraplegia or gait problems), ataxia, spasticity, hypotonia in infants, cognitive decline, vision or hearing loss, and seizures. White matter damage is evident on MRI as diffuse or patchy T2 hyperintensities.

Diagnosis combines clinical assessment with biochemical tests and genetic sequencing. Enzyme activity assays (for example ARSA in metachromatic leukodystrophy) and measurements of very long-chain fatty acids (in X-ALD) may support the diagnosis, with definitive confirmation by gene testing. Newborn screening is implemented in a few regions for select diseases.

Treatment is mainly supportive, focusing on symptom management, rehabilitation, and multidisciplinary care. In specific types, such as X-ALD, disease-modifying therapies including hematopoietic stem cell transplantation or gene therapy may slow progression if given early. Prognosis depends on the subtype and age at onset.