To determine the enzymatic defect in a patient with ataxia, dysarthric speech, dry skin, hypotonia, and absent reflexes. The patient was previously diagnosed with a presumed deficiency of trihydroxycholestanoyl-CoA oxidase.Background:
Peroxisomes harbor a variety of metabolic functions, including fatty acid β-oxidation, etherphospho-lipid biosynthesis, phytanic acid α-oxidation, and L-pipecolic acid oxidation. This patient was previously described with an isolated peroxisomal β-oxidation defect caused by a deficiency of the enzyme trihydroxycholestanoyl-CoA oxidase. This was based on the pattern of accumulating metabolites.Methods:
Measurement of β-oxidation enzymes, peroxisomal biochemical analysis in body fluids and cultured skin fibroblasts, and DNA analysis of the PEX12 gene were performed.Results:
An isolated β-oxidation defect in this patient was excluded by measurement of the various β-oxidation enzymes. The authors found that the patient had a peroxisome biogenesis disorder caused by mutations in the PEX12 gene, although all peroxisomal functions in cultured skin fibroblasts were normal.Conclusions:
The absence of clear peroxisomal abnormalities in the patient’s fibroblasts, including a normal peroxisomal localization of catalase, implies that even when all peroxisomal functions in fibroblasts are normal, a peroxisome biogenesis disorder cannot be fully excluded, and further studies may be needed. In addition, the authors’ findings imply that there is no longer evidence for the existence of trihydroxycholestanoyl-CoA oxidase deficiency as a distinct disease entity.