PEBEL1 is a rare recessive genetic condition caused by pathogenic variants in NAXE that primarily causes acute severe neurological damage in children after what would normally be a mild episode of fever, illness, or trauma. The children are born healthy with normal development, but have a rapid decline after illness. Affected infants have acute and rapid regression with ataxia, hypotonia, seizures and respiratory insufficiency. The rapidly progressing disease can lead to global brain atrophy, coma, and is often lethal. Affected individuals may develop painful skin lesions during the acute presentation.
Inheritance of PEBEL1 in nearly all cases is autosomal recessive. Pathogenic variants do not appear to be restricted to a particular type of variant, and variants have included frameshift, splicing, missense, stop gain.
There are rare instances of de novo variants (Ding, Huang et al. 2023) and homozygosity due to uniparental disomy (UPD) inheritance (Ozaki, Yatsuka et al. 2024).
NAXE