Pelizaeus-Merzbacher disease

Pelizaeus-Merzbacher disease (PMD) is a rare inherited neurological disorder classified among the hypomyelinating leukodystrophies. It is caused by mutations in the PLP1 gene located on the X chromosome, which encodes proteolipid protein 1, a major structural component of myelin in the central nervous system. Because myelin is the insulating sheath that enables efficient nerve signal transmission in the brain and spinal cord, its deficiency or abnormal formation leads to progressive neurological deterioration. PMD is also sometimes referred to as sudanophilic leukodystrophy or hypomyelinating leukodystrophy type 1 (HLD1). The disease primarily affects males, though carrier females may occasionally show mild symptoms. Clinical features typically appear in infancy and include nystagmus (involuntary rhythmic eye movements), hypotonia that progresses to spasticity, impaired motor development, ataxia (poor coordination), and cognitive impairment of variable severity. Two classical forms are recognized: the connatal (severe) form, which presents at birth or in the neonatal period with profound developmental delay, breathing difficulties, and stridor; and the classic form, which presents in early infancy with nystagmus and head tremor, followed by progressive spasticity and cerebellar dysfunction. An intermediate spectrum exists between these forms. Brain MRI characteristically shows diffuse hypomyelination of the white matter. There is currently no cure for Pelizaeus-Merzbacher disease. Treatment is supportive and symptomatic, focusing on physical therapy, occupational therapy, management of spasticity with medications such as baclofen, seizure control with antiepileptic drugs when needed, and nutritional support. Experimental approaches including stem cell transplantation and gene therapy are under investigation but remain in early stages. Life expectancy varies depending on disease severity, with the connatal form often leading to death in early childhood, while individuals with the classic form may survive into adulthood with significant disability.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Pelizaeus-Merzbacher disease