Peroxisomal disorder associated with ACOX1 gain-of-function mimicking neuroinflammatory disease

Acyl-CoA Oxidase 1 (ACOX1) catalyzes the first step of the β-oxidation of very long- chain fatty acids. We report a rare case of a peroxisomal neurodegenerative disorder associated with the c.710A>G p.(Asn237Ser) variant in ACOX1. A 6-year-old girl with a history of motor delay, presented with ichthyosiform eczema, gait disturbance, pain, weakness, areflexia, hypomimia, and hearing loss. Additional findings included albuminocytologic dissociation, enhancement of cranial nerves, spinal roots, and cervical-thoracic spinal cord. She received intravenous immunoglobulin, but subsequently developed cognitive and behavioral deterioration. Mitochondrial/peroxisomal disease was suspected. A heterozygous, likely pathogenic variant in ACOX1: NM_004035.7: c.710A>G, p.(Asn237Ser) was identified, confirming the diagnosis of Mitchell syndrome. The clinical and radiological presentation of Mitchell syndrome may initially mimic neuroinflammatory disease. However, the presence of progressive neurological deterioration, characteristic cutaneous manifestations, and hearing loss should raise suspicion of an underlying metabolic etiology. This case highlights the importance of considering Mitchell syndrome in the differential diagnosis of progressive myeloradiculopathies and polyneuropathies in pediatric patients.