Pelizaeus-Merzbacher-like disease due to HSPD1 mutation

Pelizaeus-Merzbacher-like disease due to HSPD1 mutation (also known as hypomyelinating leukodystrophy 4, or HLD4) is an extremely rare inherited neurological disorder characterized by defective formation of myelin, the protective insulating sheath that surrounds nerve fibers in the central nervous system. It is caused by mutations in the HSPD1 gene, which encodes the mitochondrial chaperonin heat shock protein 60 (HSP60), a protein essential for proper folding of mitochondrial proteins. The disease clinically resembles Pelizaeus-Merzbacher disease (PMD) but is genetically distinct, as PMD is caused by mutations in the PLP1 gene on the X chromosome. The condition primarily affects the central nervous system and manifests in infancy with progressive neurological deterioration. Key clinical features include nystagmus (involuntary eye movements), progressive spastic paraplegia (stiffness and weakness of the legs), cerebellar ataxia (impaired coordination and balance), and motor developmental delay or regression. Brain MRI typically reveals diffuse hypomyelination, reflecting the failure of normal myelin development. Cognitive impairment of variable severity may also be present. There is currently no cure or disease-specific treatment for Pelizaeus-Merzbacher-like disease due to HSPD1 mutation. Management is supportive and symptomatic, focusing on physical therapy to address spasticity and motor difficulties, occupational therapy, speech therapy, and management of complications such as seizures if they occur. The condition is classified under ICD-10 code E75.2 (other sphingolipidosis) and is listed in Orphanet under code 280288. Due to its extreme rarity, the natural history and long-term prognosis remain incompletely characterized.

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