title: Absence of the G1528C (E474Q) mutation in the alpha-subunit of the mitochondrial trifunctional protein in women with acute fatty liver of pregnancy.
abstract: Acute fatty liver of pregnancy (AFLP) is a rare and dreaded complication of pregnancy, almost exclusively seen in the third trimester. The histopathologic features of AFLP closely resemble those seen in metabolic disorders characterized by deficiency of fatty acid oxidative enzymes. Several reports have established a strong association between AFLP in the mother and fetal deficiency of the enzyme long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD). However, these studies have an inevitable selection bias resulting from ascertainment through an affected infant, rather than an unselected population of patients with AFLP. We retrospectively examined a series of 10 women with pregnancies complicated by AFLP to determine the prevalence of the common LCHAD mutation (G1528C) in this population. The existing LCHAD primers, which produce a 640-bp amplicon (IJlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ: J Clin Invest 98:1028-1033, 1996), were modified to make them amenable to analysis of fragmented DNA obtained from microdissected formalin-fixed material. None of the patients were found to harbor the common G1528C mutation. It is likely that AFLP arising in the context of fetal LCHAD deficiency represents only one of the possible etiologies for this uncommon disorder, and the metabolic basis of AFLP is more heterogeneous than previously believed.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Anibran
authors.initials: A
authors.lastname: Maitra
authors.forename: Rana
authors.initials: R
authors.lastname: Domiati-Saad
authors.forename: Nicole
authors.initials: N
authors.lastname: Yost
authors.forename: Gary
authors.initials: G
authors.lastname: Cunningham
authors.forename: Beverly Barton
authors.initials: BB
authors.lastname: Rogers
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bennett
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D000208:Acute Disease; D000328:Adult; D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D005234:Fatty Liver / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D008928:Mitochondria / Q000201:enzymology; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000235:genetics*; D020125:Mutation, Missense; D017354:Point Mutation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology* / Q000453:epidemiology; D021122:Protein Subunits; D012189:Retrospective Studies; D013781:Texas / Q000453:epidemiology
chemical_list: D009097:Multienzyme Complexes; D021122:Protein Subunits; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D063991:Mitochondrial Trifunctional Protein