Pelizaeus-Merzbacher-like disease due to AIMP1 mutation

Pelizaeus-Merzbacher-like disease due to AIMP1 mutation (also known as hypomyelinating leukodystrophy 3, or HLD3) is a rare inherited neurological disorder characterized by severe hypomyelination of the central nervous system. It is caused by biallelic mutations in the AIMP1 gene (also known as EIMP or p43), which encodes aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1. This protein plays important roles in tRNA aminoacylation and has additional functions in inflammation and neuronal development. The disease primarily affects the nervous system, leading to profound impairment of motor and cognitive development. Clinical features typically present in infancy and include severe psychomotor delay, progressive spasticity, nystagmus, ataxia, and seizures. Affected children often have difficulty achieving developmental milestones such as sitting, walking, and speaking. Brain MRI reveals diffuse hypomyelination, resembling the pattern seen in classic Pelizaeus-Merzbacher disease (which is caused by PLP1 mutations), hence the designation "Pelizaeus-Merzbacher-like." Additional features may include peripheral neuropathy and microcephaly in some patients. There is currently no cure or disease-specific treatment for this condition. Management is supportive and symptomatic, focusing on physical therapy, occupational therapy, antiepileptic medications for seizure control, and nutritional support. The prognosis is generally poor, with significant neurological disability. Genetic counseling is recommended for affected families to discuss recurrence risks and reproductive options.

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