title: Prospective screening for pediatric mitochondrial trifunctional protein defects in pregnancies complicated by liver disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yamada
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhao
authors.forename: Arnold W
authors.initials: AW
authors.lastname: Strauss
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005234:Fatty Liver / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000517:prevention & control; D017359:HELLP Syndrome / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000517:prevention & control*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011256:Pregnancy Outcome
chemical_list: D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D063991:Mitochondrial Trifunctional Protein