No mutation was found in the alpha-subunit of the mitochondrial tri-functional protein in one patient with severe acute fatty liver of pregnancy and her relatives

J Gastroenterol Hepatol. 2007 Dec;22(12):2107-11. doi: 10.1111/j.1440-1746.2006.04682.x.


Background and aim: Acute fatty liver of pregnancy (AFLP) is a serious hepatic disorder and a devastating late gestational complication associated with substantial maternal and neonatal morbidity and mortality. Several studies have demonstrated a strong association between AFLP in the mother and fetal deficiency of the enzyme long-chain L-3 hydroxyacyl-CoA dehydrogenase (LCHAD). LCHAD resides in the alpha-subunit of the mitochondrial tri-functional protein and catalyzes the third step in the beta-oxidation of fatty acids in the mitochondria. The aim of this study was to determine in one patient with severe AFLP who survived liver transplantation, if the infant or her parents would bear the common or rare mutation of the LCHAD gene.

Methods: Genomic DNA was extracted from the patient with severe AFLP and her daughter and parents. Exon 15 of LCHAD was amplified by polymerase chain reaction (PCR) and analyzed by restricted fragment length polymorphism (RFLP) with Pst-I. The whole coding region of LCHAD cDNA of all subjects was amplified and sequenced for the potential rare mutation.

Results: None of the subjects had the G1528C mutation in the LCHAD gene. None of the subjects had mutation in the whole coding region of LCHAD or rare polymorphisms.

Conclusions: Although this study was limited to one proband and her relatives, our observations suggest that there might be diverse etiological factors in China contributing to AFLP other than the frequently reported mutation in the LCHAD, and the metabolic basis for AFLP may be more heterogeneous than previously believed.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • Adult
  • Carnitine / analogs & derivatives
  • Carnitine / chemistry
  • Carnitine / metabolism
  • Cytosine
  • Family*
  • Fatty Liver / complications*
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Female
  • Guanine
  • Humans
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
  • Mass Spectrometry
  • Mitochondrial Trifunctional Protein
  • Multienzyme Complexes / genetics*
  • Mutation / genetics*
  • Polymorphism, Restriction Fragment Length
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Protein Subunits / genetics*
  • Sequence Analysis, DNA


  • Multienzyme Complexes
  • Protein Subunits
  • acylcarnitine
  • Guanine
  • Cytosine
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
  • Mitochondrial Trifunctional Protein
  • Carnitine