Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor abilities, and intellectual function deteriorate. The disease is one of a group of gene-linked disorders known as the leukodystrophies, which affect growth of the myelin sheath -- the fatty covering that wraps around and protects nerve fibers in the brain. The disease is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein (PLP). PMD is inherited as an X-linked recessive trait, in that the affected individuals are male and the mothers are carriers of the PLP mutation. Severity and onset of the disease ranges widely, depending on the type of PLP mutation, and extends from the mild, adult-onset spastic paraplegia (SPG2) to the severe form with onset at infancy and death in early childhood. The characteristic set of neurological symptoms includes nystagmus (rapid, involuntary, rhythmic jerking of the eyes and the head), spastic paraparesis (paralysis of the legs with hyperactive tendon reflexes), and limb ataxia (lack of coordination in the arms and legs). Pronounced changes in the extent of myelination can be detected by MRI analyses. Other symptoms may include slow growth, tremor, failure to develop normal control of head movement, and deteriorating speech and mental function.
There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment. Treatment, which is symptomatic and supportive, may include medication for movement disorders.
The prognosis for those with the severe forms of Pelizaeus-Merzbacher disease is poor, with progressive deterioration until death. On the other end of the disease spectrum, individuals with the mild form (in which spastic paraplegia is the chief symptom) may have nearly normal activity and life span.
Prepared by the National Institutes of Health