Pelizaeus-Merzbacher disease

Pelizaeus-Merzbacher disease is an X-linked neurological disorder in which oligodendrocytes of the central nervous system are damaged. It results from mutations in the gene for proteolipid protein 1 (PLP1), a major myelin protein, and the loss of insulating myelin around nerve fibers (hypomyelination) places it among the genetic diseases called leukodystrophies. Onset is usually in early infancy, with nystagmus and low muscle tone among the earliest signs, delayed or absent motor milestones, and later tremor, unsteady gait and spasticity. Most mutations duplicate the whole PLP1 gene, while rarer deletions cause a milder form. Classic, congenital, transitional and adult variants are described. No cure has been developed, and outcomes vary with severity.