Objective:

N/A

Background:

Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive neuro-metabolic disorder caused by a NAD(P)HX epimerase (NAXE) gene mutation leading to accumulation of toxic metabolites. This condition emerges in early childhood following febrile illness with less than 30 cases ever described. Symptoms include fluctuating ataxia, hypotonia, psychomotor regression, with eventual progression to coma and death. We present a case of PEBEL1 that was diagnosed following a respiratory illness which was initially mistaken for post-infectious cerebellar ataxia.

Design/Methods:

N/A

Results:

A 3-year-old Asian male with mild developmental delay presented to our tertiary care children’s hospital with worsening ambulation, ataxia, hypotonia, and encephalopathy. He was admitted 10 days prior at an outside hospital for abnormal gait following a respiratory illness and was tentatively diagnosed with post-infectious cerebellar ataxia with normal MRI Brain. Infectious workup including CSF studies were unrevealing. Repeat MRI of brain and spine showed new abnormal signal and diffusion restriction of the middle cerebellar peduncles with abnormal cord signal in the cervical spine concerning for a neuroinflammatory disease. Despite corticosteroids and IVIG, his condition deteriorated with worsening cerebral edema and herniation, requiring ventriculostomy. Rapid whole genome sequencing was completed, revealing a compound hemizygous mutation in the NAXE gene (one likely pathogenic allele and a single allele microdeletion of the NAXE gene) leading to the diagnosis of NAXE-associated progressive encephalopathy. Niacin supplementation was initiated with stabilization of symptoms, although he remained in static encephalopathy and ultimately required tracheostomy and gastrostomy tube placement.

Conclusions:

In children presenting with progressive ataxia and encephalopathy following a febrile illness, PEBEL1 should be on the differential diagnosis. In these cases, whole genome testing should be considered early as niacin initiation may improve clinical outcomes.