What is Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, and degenerative central nervous system disorder that deteriorates coordination, motor abilities, and cognitive function. The disease is one of a group of 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.

PMD is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1). Severity and onset of the disease ranges widely depending on the type of PLP1 mutation. PMD is one in a spectrum of diseases associated with PLP1, which also includes spastic paraplegia type 2 (SPG2). Symptoms of PLP1-related disorders range from severe central nervous system involvement to progressive weakness and stiffness of the legs.

There is no cure for PMD, 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 PMD is poor due to the progressive deterioration. Individuals with the mild form may have an average life span.

Is there any treatment?

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.

What is the prognosis?

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.

Pelizaeus-Merzbacher disease is divided into classic and severe (connatal) types. Although these two types differ in severity, their symptoms can overlap. Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking. As the child gets older, nystagmus may improve, but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements). Cognitive abilities may be impaired, but speech and language are usually present. Severe or connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms are usually present at birth or develop in the first few weeks of life. Features include nystagmus, problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures. Children often have short stature and poor weight gain. Those affected with connatal Pelizaeus-Merzbacher disease don't walk or develop effective use of their upper limbs. Verbal expression is usually severely affected, but comprehension may be significant.