Prenatal diagnosis of peroxisomal d-3-hydroxyacyl-CoA dehydratase / d-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency

The prenatal diagnosis of peroxisomal d-3-hydroxyacyl-coenzyme A (CoA) dehydratase/ d-3-hydro-xyacyl-CoA dehydrogenase bifunctional protein (d-BP) deficiency was performed by peroxisomal β-oxidation assay, indirect immunofluorescence staining, immunoblot analysis, and gene analysis of cultured amniocytes obtained from a fetus at 16 weeks' gestational age. β-Oxidation activity, measured by [1-14C] lignoceric acid oxidation, was markedly decreased compared with the controls. Large peroxisomes were readily identified by immunofluorescence staining with anti-human catalase, as was found in the reported patients. Immunoreactive d-BP material was absent on immunoblot analysis and immunofluorescence staining with anti-human d-BP. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of the same 237-bp deletion in the cDNA as that detected in a sibling (the proband). The autopsied fetus showed the characteristic facial appearance and d-BP was deficient on immunoblot and immunohistopathological studies of the fetal tissues. No neuronal migration disorder was identified. This seems to be the first prenatal diagnosis of d-BP deficiency.