Early-Onset Progressive Encephalopathy With Brain Oedema and/or Leukoencephalopathy 1: Report of three siblings

Abstract

NAXE encephalopathy, also known as early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL-1), is a rare and often lethal autosomal recessive mitochondrial disorder. Typical presentation includes psychomotor regression, ataxia, respiratory insufficiency and seizures triggered by febrile illness. This report describes three siblings from a consanguineous family who presented to a tertiary care hospital in Muscat, Oman, in 2022 and were found to have a homozygous pathogenic variant in the NAXE: NM_144772.2:c.827del, p.(Pro276Hisfs*43). Beyond the classic neuroradiological and clinical features of PEBEL-1, these patients exhibited novel phenotypic manifestations, including axonal polyneuropathy, Bull's eye maculopathy and a late-onset presentation of skin lesions. The identification of these features expands the known clinical spectrum of NAXE mutations and highlights the importance of considering this diagnosis in patients presenting with unexplained multisystemic mitochondrial symptoms involving the peripheral nerves and retina.