Peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase deficiency, also known as pseudoneonatal adrenoleukodystrophy or straight-chain acyl-CoA oxidase deficiency (ACOX1 deficiency), is a rare autosomal recessive peroxisomal fatty acid oxidation disorder. It is caused by mutations in the ACOX1 gene, which encodes the enzyme acyl-CoA oxidase 1, responsible for the first step of peroxisomal beta-oxidation of very long-chain fatty acids (VLCFAs). Deficiency of this enzyme leads to accumulation of VLCFAs in plasma and tissues, resulting in progressive damage primarily to the nervous system. Clinical features typically present in infancy and resemble neonatal adrenoleukodystrophy, hence the synonym pseudoneonatal adrenoleukodystrophy. Affected children usually appear normal at birth but develop hypotonia, seizures, and progressive loss of developmental milestones during the first years of life. Progressive white matter disease (leukodystrophy) is a hallmark finding on brain imaging. Additional features may include hearing loss, visual impairment, hepatomegaly, and failure to thrive. Biochemically, the condition is characterized by elevated plasma levels of very long-chain fatty acids, while other peroxisomal functions such as plasmalogen synthesis and phytanic acid oxidation remain normal, distinguishing it from generalized peroxisome biogenesis disorders. There is currently no curative treatment for peroxisomal acyl-CoA oxidase deficiency. Management is supportive and symptomatic, focusing on seizure control, nutritional support, physical therapy, and management of complications. The prognosis is generally poor, with most affected individuals experiencing severe neurological deterioration during childhood. Dietary restriction of very long-chain fatty acids and supplementation with Lorenzo's oil have been attempted, but their efficacy remains unproven. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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