Child Neurology: Neurodegenerative Encephalomyelopathy Associated With ACOX-1 Gain-of-Function Mutation Partially Responsive to Immunotherapy

Abstract

Acyl-CoA Oxidase 1 (ACOX1) is a peroxisomal enzyme involved in beta-oxidation of very long chain fatty acids. Although loss of function of ACOX-1 had been previously described, gain-of-function mutation of ACOX-1 gene has only been recently identified, with a paucity of known cases. Gain of function mutation results in over production of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses.

We report a 19-year-old-female with a 5-year history of longitudinally extensive posterior predominant myelopathy, bilateral corneal scars, and white matter lesions presented with first time seizure, progressive sensorineural hearing loss, icthiosyform rash, and cauda equina syndrome. Extensive work-up was unrevealing. The patient had no response to high dose steroids but stabilization and improvement with return to baseline over six months with IVIg and low dose mycophenolate mofetil. WES performed 4 years prior was non-diagnostic, but subsequent reanalysis revealed a heterozygous mutation in the ACOX1 gene (NM_004035.6: c.710A>G, p.Asn237Ser), now considered to be pathogenic.

This case reports a rare condition and highlights the importance of reanalysis of previously non-diagnostic genome/exome sequencing data. Further, the patient’s clinical stability for over one year on immunotherapy raises the possibility of disease modification in an otherwise universally fatal condition.