title: Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency.
abstract: Mitochondrial trifunctional protein (MTP) is a heterocomplex composed of 4 alpha-subunits containing LCEH (long-chain 2,3-enoyl-CoA hydratase) and LCHAD (long-chain 3-hydroxyacyl CoA dehydrogenase) activity, and 4 beta-subunits that harbor LCKT (long-chain 3-ketoacyl-CoA thiolase) activity. MTP deficiency is an autosomal recessive disorder that causes a clinical spectrum of diseases ranging from severe infantile cardiomyopathy to mild chronic progressive polyneuropathy. Here, we report the case of a Korean male newborn who presented with severe lactic acidosis, seizures, and heart failure. A newborn screening test and plasma acylcarnitine profile analysis by tandem mass spectrometry showed an increase of 3-hydroxy species: 3-OH-palmitoylcarnitine, 0.44 nmol/ml (reference range, RR <0.07); 3-OH-linoleylcarnitine, 0.31 nmol/ml (RR <0.06); and 3-OH-oleylcarnitine, 0.51 nmol/ml (RR <0.04). These findings suggested either long-chain 3-hydroxyacyl-coA dehydrogenase deficiency or complete MTP deficiency. By molecular analysis of the HADHB gene, the patient was found to be a compound heterozygote for c.358dupT (p.A120CfsX8) and c.1364T>G (p.V455G) mutations. These 2 mutations of the HADHB gene were novel and inherited. Although the patient was treated by reduction of glucose administration and supplementation of a medium-chain triglyceride-based diet with L-carnitine, he died 2 mo after birth due to advanced cardiac failure.
authors.affiliation: Department of Laboratory Medicine & Genetics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Kim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Won-Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics*; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D017240:Mitochondrial Myopathies; D024101:Mitochondrial Proteins / Q000235:genetics*; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency; D063993:Mitochondrial Trifunctional Protein, beta Subunit; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D056910:Republic of Korea; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012206:Rhabdomyolysis
chemical_list: D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; C116917:acylcarnitine; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit; D002331:Carnitine