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