Document Detail

Prospective screening for pediatric mitochondrial trifunctional protein defects in pregnancies complicated by liver disease.
MedLine Citation:
PMID:  12413376     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are serious complications of pregnancy. Studies in families with recessively inherited mitochondrial trifunctional protein defects documented an association between these maternal illnesses and fetal deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase; this enzyme resides in the alpha subunit of the trifunctional protein and catalyzes the third step in long-chain fatty acid beta oxidation.
OBJECTIVE: To estimate the frequency of fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency in pregnancies complicated by AFLP or HELLP syndrome.
DESIGN, SETTING, AND SUBJECTS: Cohort study in which 108 consecutive blood samples from women who developed AFLP or HELLP syndrome, from their offspring, or from their partners were referred to our laboratory for molecular screening from January 1997 to December 2001. Twenty-seven women had AFLP and 81 had HELLP syndrome. We screened the DNA for mutations in the alpha subunit of the trifunctional protein.
MAIN OUTCOME MEASURE: Presence of mutations that cause 3-hydroxyacyl coenzyme A dehydrogenase deficiency in the offspring.
RESULTS: We detected mutations causing pediatric long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency in 5 families (19%) with maternal history of AFLP (95% confidence interval, 9%-54%). The maternal allele carried a prevalent glutamic acid 474 to glutamine (E474Q) mutation. The paternal allele carried the E474Q mutation in 3 families and a stop codon mutation in the other 2 families. Only 1 woman with HELLP syndrome was heterozygous for the E474Q mutation; no mutations were detected in the newborn.
CONCLUSION: The association between AFLP and the E474Q mutation in the fetus is significant. Screening newborns for this mutation in pregnancies complicated by AFLP could allow early diagnosis and treatment in newborns and genetic counseling and prenatal diagnosis in subsequent pregnancies in affected families.
Zi Yang; Jennifer Yamada; Yiwen Zhao; Arnold W Strauss; Jamal A Ibdah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  JAMA     Volume:  288     ISSN:  0098-7484     ISO Abbreviation:  JAMA     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-04     Completed Date:  2002-11-14     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2163-6     Citation Subset:  AIM; IM    
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MeSH Terms
3-Hydroxyacyl CoA Dehydrogenases / deficiency*,  genetics
Cohort Studies
DNA Mutational Analysis
Fatty Liver / genetics*,  physiopathology
Fetal Diseases / genetics,  prevention & control
HELLP Syndrome / genetics*,  physiopathology
Infant, Newborn
Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
Metabolism, Inborn Errors / genetics*,  prevention & control*
Mitochondrial Trifunctional Protein
Multienzyme Complexes / genetics*,  metabolism
Polymorphism, Restriction Fragment Length
Pregnancy Complications / physiopathology*
Pregnancy Outcome
Grant Support
Reg. No./Substance:
0/Multienzyme Complexes; EC 1.1.1.-/3-Hydroxyacyl CoA Dehydrogenases; EC Dehydrogenase; EC Trifunctional Protein
Comment In:
Gastroenterology. 2003 May;124(5):1548-50; discussion 1550   [PMID:  15534983 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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