Peroxisomal acyl-CoA-oxidase deficiency. Pseudoneonatal adrenoleukodystrophy . Pseudo-NALD. ACOX1 .
Incidence
It is a rare condition. Autosomal recessive inheritance. Caused by mutations in the peroxisomal acyl-CoA oxidase gene (ACOX1). Less than 40 cases reported.
Clinical Characteristics
The initial report on this condition was done by Poll-The et al. (1988) when they reported a brother and sister, born of first-cousin parents, with neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression after age 2 years. Brain imaging showed progressive white-matter demyelination without cortical malformations. Biochemical analysis showed accumulation of very long chain fatty acids (VLCFA) resulting from an isolated deficiency of peroxisomal fatty acyl-CoA oxidase. The clinical findings resembled neonatal adrenoleukodystrophy, but liver biopsy showed that hepatic peroxisomes were not decreased in number and were enlarged in size. In addition, there was no accumulation of pipecolic acid or bile acid synthesis intermediates, and there was no marked decrease in plasmalogens. Peroxisomal acyl-CoA oxidase deficiency or Pseudo-NALD is a peroxisomal single-enzyme disorder. It is a disorder of peroxisomal fatty acid beta-oxidation. Onset in early infancy. Neurologic deterioration is severe after age 2 to 2.5 years. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Ferdinandusse et al. (2007) reported 22 patients with acyl-CoA oxidase deficiency confirmed by genetic analysis. Clinical features included hypotonia, seizures, failure to thrive, visual system failure, impaired hearing and vision, loss of motor achievements, hepatomegaly, dysmorphism, brain white matter abnormalities, and osteopenia. The mean age of developmental regression was 28 months, and the mean age at death was 5 years. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
Increased plasma levels of very-long chain fatty acids (VLCFA). Decreased or absent peroxisome acyl-CoA oxidase activity and protein. Normal serum plasmalogen. Genetic testing show mutations in the peroxisomal acyl-CoA oxidase gene (ACOX1).