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An investigation into the aetiology of acute fatty liver of pregnancy

Kaler, Mandeep Kaur; (2018) An investigation into the aetiology of acute fatty liver of pregnancy. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Acute fatty liver of pregnancy (AFLP) is a rare, but devastating gestational syndrome. Women with AFLP present in the third trimester with the clinical and biochemical characteristics of a defect in energy metabolism. A minority of AFLP cases are associated with a defect in mitochondrial fatty acid oxidation (LCHAD deficiency). The main aim of my thesis is to discover whether women who have had AFLP, but who do not have LCHAD deficiency, have an alternative subclinical defect in fat metabolism. I firstly studied the clinical records of 33 women who had AFLP. None of the women (n=28) nor 5 offspring of the remaining 5 women had the common LCHAD gene variant. Only 19 of these women had urinalysis at the time of presentation and despite prolonged starvation, none of them had ketonuria. This observation supported my hypothesis that AFLP is associated with a defect in fatty acid oxidation (FAO). Having confirmed that fasting during the third trimester of healthy pregnancy leads to accelerated ketosis, I tested the hypothesis that non-pregnant women who had AFLP have a sub-clinical defect in fat metabolism. Following a 24-hour fast and fatburning exercise, women who had AFLP (n=13) generated ketones at a similar rate to 23 women who had not had AFLP. Furthermore, a proteomic analysis showed no difference in 1300 serum proteins between women who had AFLP and those who had a normal pregnancy. The whole exome sequence (3 AFLP families) and whole genome sequence (4 AFLP families), did not identify any novel gene variants associated with defective energy metabolism. My results suggest AFLP is a pregnancy-specific defect in maternal fatty acid oxidation, which has no latent impact on maternal FAO. The study of women with AFLP during pregnancy is necessary to identify altered concentrations of a pregnancy-specific factor that inhibits maternal FAO.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: An investigation into the aetiology of acute fatty liver of pregnancy
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2018. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10063829
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