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Role of genetic screening in identifying susceptibility to acute fatty liver of pregnancy

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 494–495 (2005)Cite this article

Acute fatty liver of pregnancy (AFLP) is a devastating disorder of the third trimester that carries a significant neonatal and maternal morbidity and mortality. Its prevalence is approximately 1 in every 13,000 deliveries.1 Histologically, it is characterized by microvesicular hepatic steatosis. The cornerstones in the management of this condition are early diagnosis and prompt delivery. HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome is also a maternal illness of the third trimester but has a better prognosis than AFLP. It is estimated to occur in 0.1–0.6% of all pregnancies.1 In patients with this condition, liver biopsy shows periportal hemorrhage and fibrin deposition. Similarly to AFLP, prompt delivery is the treatment of choice. In some women, differentiation of HELLP syndrome and AFLP can be difficult without liver biopsy, owing to a significant overlap in the clinical and biochemical features of the two conditions.

The first evidence to suggest that an underlying defect in fatty-acid oxidation might contribute to the pathogenesis of these pregnancy-associated liver diseases was provided by Schoeman et al., who reported a case of a woman with recurrent AFLP who gave birth to offspring with an ill-defined abnormality of fatty-acid oxidation.2 β-oxidation of fatty acids is the major source of energy for skeletal muscle and the heart, and plays an essential role in intermediary metabolism in the liver. There are four reactions in the β-oxidation spiral mediated successively by acyl-CoA dehydrogenase, long-chain enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. The mitochondrial trifunctional protein (MTP) is a hetero-octamer of 4 α-subunits and 4 β-subunits associated with the inner mitochondrial membrane. The α-subunit contains the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activities, and the β-subunit contains the long-chain 3-ketoacyl-CoA thiolase activity. MTP gene defects are recessively inherited. Biochemical studies have identified two groups of patients who are MTP-deficient;3 the first has an isolated LCHAD deficiency and the second has a complete MTP deficiency. Patients who are LCHAD-deficient often present at a few months of age with an acute Reye-like syndrome of nonketotic hypoglycemia and hepatic encephalopathy, which can progress to coma and death if untreated.3 The prevalence of LCHAD deficiency seems to be higher in the US, with a carrier frequency of 1:175 as compared with other countries, such as Finland (1:240) or Holland (1:680).

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  1. Medical Pharmacology & Physiology and the Director of the Division of Gastroenterology and Hepatology at the University of Missouri–Columbia, Professor of Medicine, MO, USA

    Jamal A Ibdah

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  1. Jamal A Ibdah
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Ibdah, J. Role of genetic screening in identifying susceptibility to acute fatty liver of pregnancy. Nat Rev Gastroenterol Hepatol 2, 494–495 (2005). https://doi.org/10.1038/ncpgasthep0287

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