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-1 (PLP1). PMD is inherited as an X-linked recessive trait; the affected individuals are male and the mothers are carriers of the PLP1 mutation. Severity and onset of the disease ranges widely, depending on the type of PLP1 mutation. PMD is one of a spectrum of diseases associated with PLP1, which also includes Spastic Paraplegia Type 2 (SPG2). The PLP1-related disorders span a continuum of neurologic symptoms that range from severe central nervous system involvement (PMD) to progressive weakness and stiffness of the legs (SPG2).
There are four general classifications within this spectrum of diseases. In order of severity, they are:
- Connatal PMD, which is the most severe type and involves delayed mental and physical development and severe neurological symptoms;
- Classic PMD, in which the early symptoms include muscle weakness, involuntary movements of the eyes (nystagmus), and delays in motor development within the first year of life;
- Complicated SPG2, which features motor development issues and brain involvement, and,
- Pure SPG2, which includes cases of PMD that do not have neurologic complications.
Noticeable changes in the extent of myelination can be detected by MRI analyses of the brain. Additional symptoms of PMD may include slow growth, tremor, failure to develop normal control of head movement, and deteriorating speech and cognitive function.
There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment. Treatment is symptomatic and supportive and 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.
NINDS supports research on gene-linked disorders, including the leukodystrophies. The goals of this research are to increase scientific understanding of these disorders and to find ways to prevent, treat, and ultimately cure them. Information from the National Library of Medicine’s MedlinePlusGenetics Home Reference: Pelizaeus-Merzbacher disease
Hunter's Hope Foundation[A Leukodystrophy Resource]
P.O. Box 643
21 Princeton Plaza, Suite 12
Orchard Park, NY 14127
Fosters awareness about Krabbe disease and other leukodystrophies, works to promote early detection through newborn screening, provides information and service linkages to families, and funds research efforts to identify new treatments and therapies, and ultimately, a cure.
P.O. Box 39
Pacific Palisades, CA 90272
Aims to accelerate research on repair of myelin, the white matter insulating the nerves, which can be destroyed by hereditary metabolic disorders, such as the leukodystrophies, and acquired disorders, such as multiple sclerosis.
PMD Foundation (Pelizaeus-Merzbacher disease)
P.O. Box 898
Salado, TX 76751
Tax-exempt, nonprofit organization that serves families, researchers, and others affected by Pelizaeus-Merzbacher disease by supporting education, research, services, and advocacy programs.
Information sourced through CNF’s partnership with The National Institute of Neurological Disorders and Stroke (NINDS), US National Institutes of Health.