Back to Search
Start Over
A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.
A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.
- Source :
-
The New England journal of medicine [N Engl J Med] 1999 Jun 03; Vol. 340 (22), pp. 1723-31. - Publication Year :
- 1999
-
Abstract
- Background: Acute fatty liver of pregnancy and the HELLP syndrome (hemolysis, elevated liver-enzyme levels, and a low platelet count) are serious hepatic disorders that may occur during pregnancy in women whose fetuses are later found to have a deficiency of long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase. This enzyme resides in the mitochondrial trifunctional protein, which also contains the active site of long-chain 2,3-enoyl-CoA hydratase and long-chain 3-ketoacyl-CoA thiolase. We undertook this study to determine the relation between mutations in the trifunctional protein in infants with defects in fatty-acid oxidation and acute liver disease during pregnancy in their mothers.<br />Methods: In 24 children with 3-hydroxyacyl-CoA dehydrogenase deficiency, we used DNA amplification and nucleotide-sequence analyses to identify mutations in the alpha subunit of the trifunctional protein. We then correlated the results with the presence of liver disease during pregnancy in the mothers.<br />Results: Nineteen children had a deficiency only of long-chain 3-hydroxyacyl-CoA dehydrogenase and presented with hypoketotic hypoglycemia and fatty liver. In eight children, we identified a homozygous mutation in which glutamic acid at residue 474 was changed to glutamine. Eleven other children were compound heterozygotes, with this mutation in one allele of the alpha-subunit gene and a different mutation in the other allele. While carrying fetuses with the Glu474Gln mutation, 79 percent of the heterozygous mothers had fatty liver of pregnancy or the HELLP syndrome. Five other children, who presented with neonatal dilated cardiomyopathy or progressive neuromyopathy, had complete deficiency of the trifunctional protein (loss of activity of all three enzymes). None had the Glu474Gln mutation, and none of their mothers had liver disease during pregnancy.<br />Conclusions: Women with acute liver disease during pregnancy may have a Glu474Gln mutation in long-chain hydroxyacyl-CoA dehydrogenase. Their infants are at risk for hypoketotic hypoglycemia and fatty liver.
- Subjects :
- 3-Hydroxyacyl CoA Dehydrogenases genetics
Acute Disease
DNA Mutational Analysis
Female
Genotype
Humans
Infant
Infant, Newborn
Lipid Metabolism, Inborn Errors genetics
Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
Mitochondria metabolism
Mitochondrial Trifunctional Protein
Multienzyme Complexes genetics
Mutation
Oxidation-Reduction
Pregnancy
Fatty Acids metabolism
Fatty Liver etiology
Fetal Diseases genetics
HELLP Syndrome etiology
Lipid Metabolism, Inborn Errors complications
Multienzyme Complexes deficiency
Pregnancy Complications etiology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-4793
- Volume :
- 340
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 10352164
- Full Text :
- https://doi.org/10.1056/NEJM199906033402204