A homozygous pathogenic variant causes a fatal congenital neuropathy.

Background: UBA5 is the activating enzyme of UFM1 in the ufmylation post-translational modification system. Different neurological phenotypes have been associated with pathogenic variants including epilepsy, intellectual disability, movement disorders and ataxia.

Methods And Results: We describe a large multigenerational consanguineous family presenting with a severe congenital neuropathy causing early death in infancy.