General description

EPRS1-associated hypomyelinating leukodystrophy, also known as hypomyelinating leukodystrophy 15 (HLD15), is an autosomal recessive genetic disorder caused by mutations in the EPRS1 gene, which encodes a bifunctional aminoacyl-tRNA synthetase responsible for catalyzing the aminoacylation of glutamic acid and proline tRNA species. These mutations lead to reduced translation capacity in the central nervous system, resulting in insufficient myelination and hypomyelinating leukodystrophy.

The disease typically manifests in infancy with microcephaly and developmental delays, including motor and intellectual impairments. Affected individuals may experience ataxia, dystonia, pyramidal tract signs, and sensorineural hearing loss. Severe cases lead to difficulties in swallowing, requiring gastrostomy feeding, and most patients do not achieve independent walking. Life expectancy is significantly reduced, with death occurring by early childhood.