Pelizaeus Merzbacher Disease (PMD)

PMD is caused by a mutation in the gene PLP1, this gene is x-linked chromosome in band xq22. X-linked pattern of inheritance with boys who have mutation; occasionally females have a mild or moderate form of symptoms, females with mutation are carriers of the disease. PLP1 (proteolipid protein) in the myelin sheath results in the demyelination (loss of myelin). Severity depends on the mutation of the PLP1, levels can range from early lethal forms to a mild disorder known as spastic paraplegia type 2 (SPG2).

PMD classically manifests in infancy/childhood and progresses to severe spasticity and ataxia. The life span is shortened. PMD in early infancy is referred to as connatal PMD, Typical symptoms are; early on floppy muscles (hypotonia), Nystagmus (rhythmical oscillation of eyes), impaired motor development, tremor, progressive spasticity (increased muscle tone), ataxia (wobbliness), choreathetotic movements, dysartria (difficulty speaking).

Children who have Classical PMD, which is a less severe form than Connatal PMD, usually have Nystagmus (jerking of the eyes) within the first few months and other symptoms within the first few years, these children also have hypotonia which will then turn in to spasticity. Sometimes children can learn to walk, titubation (shaking of the head & neck) may also occur, these children often have moderate mental retardation, often learning to talk and understanding more than their speech allows.

A less severe type of PMD is referred to as PLP Null Syndrome, those affected do not usually have nystagmus and their spasticity is mild, symptoms usually develop in early childhood and may have peripheral neuropathy (problems with the nerves that run from the spinal cord through out the body), this can cause weakness and problems with sensations i.e. hot & cold, usually have mild to moderate mental retardation.

Boys with Connatal PMD may die in early infancy or early childhood, although some have survived into their 30s. Classical PMD or PLP null syndrome usually reach adulthood and some have been known to survive into their 70s, symptoms of PMD usually progress slowly. The speed and progression of PMD does vary, from patient to patient.

At present there is no treatment or cure, only symptomatic treatment and support can be offered.