RGD Reference Report - The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. - Rat Genome Database

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The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.

Authors: Sims, HF  Brackett, JC  Powell, CK  Treem, WR  Hale, DE  Bennett, MJ  Gibson, B  Shapiro, S  Strauss, AW 
Citation: Sims HF, etal., Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):841-5.
RGD ID: 1599882
Pubmed: PMID:7846063   (View Abstract at PubMed)
PMCID: PMC42716   (View Article at PubMed Central)

Mitochondrial long chain fatty acid beta-oxidation provides the major source of energy in the heart. Deficiencies of human beta-oxidation enzymes produce sudden, unexplained death in childhood, acute hepatic encephalopathy, skeletal myopathy, or cardiomyopathy. Long chain 3-hydroxyacyl-CoA dehydrogenase [LCHAD; long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase, EC 1.1.1.211] catalyzes the third step in beta-oxidation, and this activity is present on the C-terminal portion of the alpha subunit of mitochondrial trifunctional protein. We used single-stranded conformation variance analysis of the exons of the human LCHAD (alpha subunit) gene to determine the molecular basis of LCHAD deficiency in three families with children presenting with sudden unexplained death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). In all families, the mothers had acute fatty liver and associated sever complications during pregnancies with the affected infants. The analysis in two affected children revealed a G to C mutation at position 1528 (G1528C) of the alpha subunit of the trifunctional protein on both alleles. This is in the LCHAD domain and substitutes glutamine for glutamic acid at position 474 of mature alpha subunit. The third child had this G1528C mutation on one allele and a different mutation (C1132T) creating a premature termination codon (residue 342) on the second allele. Our results demonstrate that mutations in the LCHAD domain of the trifunctional protein alpha subunit in affected offspring are associated with maternal acute fatty liver of pregnancy. This is the initial delineation of the molecular basis of isolated LCHAD deficiency.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
steatotic liver disease  IAGP 1599882DNA:point mutations: more ...RGD 
steatotic liver disease  ISOHADHA (Homo sapiens)1599882; 1599882DNA:point mutations: more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hadha  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)

Genes (Mus musculus)
Hadha  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)

Genes (Homo sapiens)
HADHA  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)


Additional Information