Abstract for presentation at 11th International Congress of Human Genetics

The human mitochondrial trifunctional protein (MTP) is a heterocomplex containing four α and four β-subunits, which are encoded by two nuclear genes. The α-subunit harbors both enoyl CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activities whereas the β-subunit is responsible for 3-keto-acyl-CoA thiolase activity. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, an autosomal recessive disorder, is clinically characterized by hypoglycemia, hypotonia, hepatomegaly, cardiomyopathy, or sudden unexplained infant death. In this study, six unrelated patients (probands) with LCHAD deficiency had recently been investigated. In vitro probe analysis with [16-²H₃] palmitic acid from the probands’ fibroblasts resulted in labeled acylcarnitines consistent with LCHAD deficiency. To investigate the molecular aspect, the common mutation 1528G>C had been tested firstly, Five probands are compound heterozygous for 1528 G>C. To screen for unknown mutations within the MTP gene, particularly in α-subunit, all exons and their flanking intronic sequences were amplified from probands’ DNA. The PCR products were purified and sequenced. Sequence analysis revealed seven mutations, including novel mutations such as 2111C>T. All mutations were also verified by a PCR/restriction test, but were not detected in the normal control subjects. The genotype and clinical phenotype of LCHAD deficiency was also discussed.