Clinical Summary

  • Disorder: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1)
  • Inheritance: Autosomal recessive
  • Pathophysiology: Severe neurometabolic disorder characterized by impaired NAD(P)H repair due to NAXE mutations
  • Clinical Course: Rapid neurologic deterioration typically associated with a febrile illness
  • Developmental Pattern: Normal early development followed by acute psychomotor regression
  • Key Neurological Features: Ataxia, hypotonia, seizures, respiratory insufficiency, and progression to coma
  • Prognosis: High early mortality; death often occurs within the first few years of life
  • Neuroimaging Findings: Brain edema and signal abnormalities in cortical and subcortical white matter regions

Clinical Features of PEBEL1

Age of Onset & Triggers

  • Normal early development followed by acute regression typically in late infancy or toddlerhood (median onset ~1.2 years).
  • Episodes are often precipitated by:
    • Trivial febrile illnesses
    • Routine vaccinations

    Neurologic Manifestations