Nuclear Mitochondrial Disorder Due to a Variant in NAXE in Two Unrelated Indian Children

Progressive encephalopathy with brain edema and/or leukoencephalopathy type 1 (PEBEL1) is a nuclear mitochondrial disorder involving the NAD(P)HX repair mechanism due to a NAXE variation. PEBEL1 is characterized by rapid neurologic deterioration culminating in death following high-grade fever during infancy. Currently, 23 patients from 14 families are described in the literature, with only three survivors. The authors report two living children from unrelated families with PEBEL1. Both children presented in infancy with ptosis, squint, and ataxia with no skin manifestations. Whole-exome sequencing revealed previously reported c.804_807delInsA (p.Lys270del) variation in exon 6 of NAXE. This is the first Indian report of PEBEL1.

Automated summary

Progressive encephalopathy with brain edema and/or leukoencephalopathy type 1 (PEBEL1) is a rare mitochondrial disorder caused by NAXE gene variation, leading to impaired repair mechanism. Patients usually experience rapid neurological deterioration and death after high-grade fever in infancy. Limited cases have been reported and survival rate is low. This study presents two surviving infants with PEBEL1 from unrelated Indian families and contributes to the understanding of this disease.