Child Neurology: Neurodegenerative Encephalomyelopathy Associated With <i>ACOX1</i> Gain-of-Function Variation 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 <i>ACOX1</i> had been previously described, gain-of-function variation of <i>ACOX1</i> gene has been only recently identified, with a paucity of known cases. Gain-of-function variation results in overproduction of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses. We report the case of a 19-year-old woman with a 5-year history of longitudinally extensive posterior predominant myelopathy, bilateral corneal scars, and white matter lesions who presented with first-time seizure, progressive sensorineural hearing loss, ichthyosiform rash, and cauda equina syndrome. Extensive workup was unrevealing. The patient showed no response to high-dose steroids but stabilization and improvement with return to baseline over 6 months with IVIg and low-dose mycophenolate mofetil. Whole-exome sequencing performed 4 years before was nondiagnostic, but subsequent reanalysis revealed a heterozygous variation in the <i>ACOX1</i> gene (NM_004035.6: c.710A&gt;G, p.Asn237Ser), now considered to be pathogenic. This case reports a rare condition and highlights the importance of reanalysis of previously nondiagnostic genome/exome sequencing data. Furthermore, the patient9s clinical stability for over 1 year on immunotherapy raises the possibility of disease modification in an otherwise universally fatal condition.

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