Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional
Y Suzuki1, Z Zhang, N Shimozawa
1Department of Pediatrics, Gifu University School of Medicine, Japan. ysuz@cc.gifu-u.ac.jp
Insights
This study reports the first prenatal diagnosis of peroxisomal D-3-hydroxyacyl-coenzyme A (CoA) dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP) deficiency. Prenatal testing confirmed D-BP deficiency in a fetus at 16 weeks gestation.
Area of Science:
- Biochemistry
- Genetics
- Peroxisomal Disorders
Background:
- Peroxisomal D-3-hydroxyacyl-coenzyme A (CoA) dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP) deficiency is a rare genetic disorder.
- Prenatal diagnosis is crucial for early intervention and management.
Observation:
- Cultured amniocytes from a 16-week fetus were analyzed using various techniques.
- Peroxisomal beta-oxidation was significantly reduced, and large peroxisomes were observed.
Findings:
- Immunoreactive D-BP was absent, and a specific cDNA deletion was identified, confirming D-BP deficiency.
- Autopsy of the fetus revealed characteristic facial features and confirmed D-BP deficiency in tissues.
Implications:
- This marks the first successful prenatal diagnosis of D-BP deficiency.
- Early prenatal detection enables timely management strategies for affected newborns.
Abstract:
The prenatal diagnosis of peroxisomal D-3-hydroxyacyl-coenzyme A (CoA) dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP) deficiency was performed by peroxisomal beta-oxidation assay, indirect immunofluorescence staining, immunoblot analysis, and gene analysis of cultured amniocytes obtained from a fetus at 16 weeks' gestational age. beta-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.
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