Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency

William R. Treem, Marie E. Shoup, Daniel Hale, Michael J. Bennett, Piero Rinaldo, David S. Millington, Charles A. Stanley, Caroline A. Riely, Jeffrey S. Hyams

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Background: The similarity of the hepatic pathology in acute fatty liver of pregnancy (AFLP) to that seen in children with inherited disorders of intramitochondrial fatty acid oxidation (FAO) suggests that there may be a genetic basis for some cases of AFLP. Objective: The purpose of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for the FAO defect, long chain 3- hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. Methods: We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of their cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts from AFLP patients, their children, and their husbands were also examined specifically for LCHAD activity. Results: Of 12 women with a previous episode of AFLP, eight had reduced LCHAD activity consistent with being heterozygous for LCHAD deficiency. The eight heterozygotes had a total of nine pregnancies complicated by AFLP. In seven of those nine pregnancies, the women developed severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Of the nine offspring delivered from these pregnancies, four were confirmed to be affected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD- deficient based on clinical findings, postmortem examination, and confirmed heterozygote parents. The remaining two infants delivered after pregnancies complicated by AFLP had LCHAD activity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this defect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity. Conclusions: These studies indicate that a significant subgroup of women with AFLP are heterozygous for LCHAD deficiency and that careful observation of their offspring for signs of this disorder is warranted. Severe preeclampsia appears to increase the risk of AFLP in LCHAD heterozygous women.

Original languageEnglish (US)
Pages (from-to)2293-2300
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume91
Issue number11
StatePublished - Nov 1 1996

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3-Hydroxyacyl CoA Dehydrogenases
Hemolysis
Blood Platelets
Liver
Enzymes
Pregnancy
Fatty Acids
Heterozygote
Pre-Eclampsia
Spouses
Skin
Trifunctional Protein Deficiency With Myopathy And Neuropathy
Acute fatty liver of pregnancy
3-Hydroxyacyl-CoA Dehydrogenase
Fibroblasts
Autopsy
Fasting

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Treem, William R. ; Shoup, Marie E. ; Hale, Daniel ; Bennett, Michael J. ; Rinaldo, Piero ; Millington, David S. ; Stanley, Charles A. ; Riely, Caroline A. ; Hyams, Jeffrey S. / Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. In: American Journal of Gastroenterology. 1996 ; Vol. 91, No. 11. pp. 2293-2300.
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title = "Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency",
abstract = "Background: The similarity of the hepatic pathology in acute fatty liver of pregnancy (AFLP) to that seen in children with inherited disorders of intramitochondrial fatty acid oxidation (FAO) suggests that there may be a genetic basis for some cases of AFLP. Objective: The purpose of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for the FAO defect, long chain 3- hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. Methods: We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of their cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts from AFLP patients, their children, and their husbands were also examined specifically for LCHAD activity. Results: Of 12 women with a previous episode of AFLP, eight had reduced LCHAD activity consistent with being heterozygous for LCHAD deficiency. The eight heterozygotes had a total of nine pregnancies complicated by AFLP. In seven of those nine pregnancies, the women developed severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Of the nine offspring delivered from these pregnancies, four were confirmed to be affected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD- deficient based on clinical findings, postmortem examination, and confirmed heterozygote parents. The remaining two infants delivered after pregnancies complicated by AFLP had LCHAD activity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this defect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity. Conclusions: These studies indicate that a significant subgroup of women with AFLP are heterozygous for LCHAD deficiency and that careful observation of their offspring for signs of this disorder is warranted. Severe preeclampsia appears to increase the risk of AFLP in LCHAD heterozygous women.",
author = "Treem, {William R.} and Shoup, {Marie E.} and Daniel Hale and Bennett, {Michael J.} and Piero Rinaldo and Millington, {David S.} and Stanley, {Charles A.} and Riely, {Caroline A.} and Hyams, {Jeffrey S.}",
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Treem, WR, Shoup, ME, Hale, D, Bennett, MJ, Rinaldo, P, Millington, DS, Stanley, CA, Riely, CA & Hyams, JS 1996, 'Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency', American Journal of Gastroenterology, vol. 91, no. 11, pp. 2293-2300.

Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. / Treem, William R.; Shoup, Marie E.; Hale, Daniel; Bennett, Michael J.; Rinaldo, Piero; Millington, David S.; Stanley, Charles A.; Riely, Caroline A.; Hyams, Jeffrey S.

In: American Journal of Gastroenterology, Vol. 91, No. 11, 01.11.1996, p. 2293-2300.

Research output: Contribution to journalArticle

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T1 - Acute fatty liver of pregnancy, hemolysis, elevated liver enzymes, and low platelets syndrome, and long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency

AU - Treem, William R.

AU - Shoup, Marie E.

AU - Hale, Daniel

AU - Bennett, Michael J.

AU - Rinaldo, Piero

AU - Millington, David S.

AU - Stanley, Charles A.

AU - Riely, Caroline A.

AU - Hyams, Jeffrey S.

PY - 1996/11/1

Y1 - 1996/11/1

N2 - Background: The similarity of the hepatic pathology in acute fatty liver of pregnancy (AFLP) to that seen in children with inherited disorders of intramitochondrial fatty acid oxidation (FAO) suggests that there may be a genetic basis for some cases of AFLP. Objective: The purpose of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for the FAO defect, long chain 3- hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. Methods: We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of their cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts from AFLP patients, their children, and their husbands were also examined specifically for LCHAD activity. Results: Of 12 women with a previous episode of AFLP, eight had reduced LCHAD activity consistent with being heterozygous for LCHAD deficiency. The eight heterozygotes had a total of nine pregnancies complicated by AFLP. In seven of those nine pregnancies, the women developed severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Of the nine offspring delivered from these pregnancies, four were confirmed to be affected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD- deficient based on clinical findings, postmortem examination, and confirmed heterozygote parents. The remaining two infants delivered after pregnancies complicated by AFLP had LCHAD activity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this defect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity. Conclusions: These studies indicate that a significant subgroup of women with AFLP are heterozygous for LCHAD deficiency and that careful observation of their offspring for signs of this disorder is warranted. Severe preeclampsia appears to increase the risk of AFLP in LCHAD heterozygous women.

AB - Background: The similarity of the hepatic pathology in acute fatty liver of pregnancy (AFLP) to that seen in children with inherited disorders of intramitochondrial fatty acid oxidation (FAO) suggests that there may be a genetic basis for some cases of AFLP. Objective: The purpose of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for the FAO defect, long chain 3- hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. Methods: We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of their cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts from AFLP patients, their children, and their husbands were also examined specifically for LCHAD activity. Results: Of 12 women with a previous episode of AFLP, eight had reduced LCHAD activity consistent with being heterozygous for LCHAD deficiency. The eight heterozygotes had a total of nine pregnancies complicated by AFLP. In seven of those nine pregnancies, the women developed severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Of the nine offspring delivered from these pregnancies, four were confirmed to be affected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD- deficient based on clinical findings, postmortem examination, and confirmed heterozygote parents. The remaining two infants delivered after pregnancies complicated by AFLP had LCHAD activity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this defect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity. Conclusions: These studies indicate that a significant subgroup of women with AFLP are heterozygous for LCHAD deficiency and that careful observation of their offspring for signs of this disorder is warranted. Severe preeclampsia appears to increase the risk of AFLP in LCHAD heterozygous women.

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