PMID- 10077518
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20220419
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 99
IP  - 10
DP  - 1999 Mar 16
TI  - Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency
      causing pediatric cardiomyopathy and sudden death.
PG  - 1337-43
AB  - BACKGROUND: Genetic defects are being increasingly recognized in the etiology of 
      primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD)
      catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism,
      the crucial pathway for cardiac energy production. METHODS AND RESULTS: We
      studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction,
      skeletal myopathy, or sudden death in infancy with hepatic steatosis, features
      suggestive of fatty acid oxidation disorders. Single-stranded conformational
      variance was used to screen genomic DNA. DNA sequencing and mutational analysis
      revealed 21 different mutations on the VLCAD gene in 18 patients. Of the
      mutations, 80% were associated with CM. Severe CM in infancy was recognized in
      most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA
      blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in 
      patients with frame-shift or splice-site mutations and absent or severe reduction
      in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical 
      phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are
      heterogeneous. Although mortality at presentation is high, both the metabolic
      disorder and cardiomyopathy are reversible.
FAU - Mathur, A
AU  - Mathur A
AD  - Departments of Pediatrics, Medicine and Molecular Biology and Pharmacology,
      Washington University School of Medicine, St Louis Children's Hospital, St Louis,
      MO, USA.
FAU - Sims, H F
AU  - Sims HF
FAU - Gopalakrishnan, D
AU  - Gopalakrishnan D
FAU - Gibson, B
AU  - Gibson B
FAU - Rinaldo, P
AU  - Rinaldo P
FAU - Vockley, J
AU  - Vockley J
FAU - Hug, G
AU  - Hug G
FAU - Strauss, A W
AU  - Strauss AW
LA  - eng
GR  - DK33487/DK/NIDDK NIH HHS/United States
GR  - HL-52350/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - EC 1.3.- (Acyl-CoA Dehydrogenases)
RN  - EC 1.3.8.8 (Acyl-CoA Dehydrogenase, Long-Chain)
SB  - IM
MH  - Acyl-CoA Dehydrogenase, Long-Chain
MH  - Acyl-CoA Dehydrogenases/chemistry/*deficiency/genetics
MH  - Amino Acid Substitution
MH  - Cardiomyopathies/enzymology/genetics
MH  - Cell Line
MH  - Death, Sudden, Cardiac/*etiology
MH  - Energy Metabolism
MH  - Fatty Liver/enzymology/genetics
MH  - Female
MH  - Fibroblasts/enzymology
MH  - Frameshift Mutation
MH  - Humans
MH  - Hypoglycemia/enzymology/genetics
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Models, Molecular
MH  - *Mutation
MH  - Myocardium/enzymology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - RNA Splicing
MH  - Sudden Infant Death/*etiology
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - 10.1161/01.cir.99.10.1337 [doi]
PST - ppublish
SO  - Circulation. 1999 Mar 16;99(10):1337-43. doi: 10.1161/01.cir.99.10.1337.