Summary
Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and that is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy. Acyl-CoA oxidase deficiency is a relatively rare disease with only 30-40 patients identified world-wide so far. The disease manifests in the neonatal period with hypotonia (92%) and seizures (91%) as dominant features. Facial dysmorphism (50%) with hypertelorism, epicanthus, low nasal bridge, and low-set ears may be present. Some children have polydactyly and hepatomegaly. Psychomotor development is delayed, but children achieve usually walking and speaking a few words. However, neurological regression occurs usually at the age of 1-3 years (mean age: 28 months). Hypotonia changes into hypertonia with hyperreflexia. Epilepsy may become more severe and sensorineural hearing loss may appear. Strabismus, nystagmus, and optic atrophy can also occur. Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene (17q25.1) encoding peroxisomal straight-chain acyl-CoA oxidase. Transmission is autosomal recessive. Diagnosis is based on laboratory studies revealing increased serum very-long chain fatty acids (VLCFA) and markedly reduced acyl-CoA oxidase activity in fibroblasts. MRI exams of the brain show abnormal white matter signals. DNA confirmation by revealing mutations in the ACOX1 gene is possible. Differential diagnoses include Usher syndrome (see this term) and all causes of neonatal hypotonia. The other peroxisomal disorders should also be discarded, especially neonatal adrenoleukodystrophy that present similar clinical manifestations (see this term). Antenatal diagnosis is possible through biochemical and/or molecular analysis of amniocytes or chorionic villus cells. Genetic counseling should be offered to the patient's families. No specific treatment is available. Multidisciplinary supportive care should be offered to the patients. Prognosis is unfavorable; death usually occurs at around 5 years from respiratory issues.*Author: Prof. R.J.A. Wanders (February 2010)*.
