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Title: An investigation into the aetiology of acute fatty liver of pregnancy
Author: Kaler, Mandeep Kaur
ISNI:       0000 0004 7659 9195
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available