Screening of Acylcarnitines in Mothers and Babies in Acute fatty liver

  • Research type

    Research Study

  • Full title

    Screening for newborn fatty oxidation defects using Acylcarnitines in Mothers and Babies in Acute fatty liver of pregnancy and HELLP syndrome (SAMBA)

  • IRAS ID

    66879

  • Contact name

    Karen Ignatian

  • Contact email

    karen.ignatian@gstt.nhs.uk

  • Sponsor organisation

    Guys and St Thomas' NHS Foundation Trust (GSTT)

  • Research summary

    Fatty acids play a critical role in supplying energy during fasting and stress. Fatty acid oxidation defects (FAOD) are caused by rare genetic defects which can be potentially fatal. Early identification can prevent developmental delay, liver, cardiac and neurological complications in the newborn. Every baby that is born in the UK is tested for a number of rare metabolic diseases including a more common fatty acid oxidation disorder called medium chain 3-hydroxyacyl coenzyme-A dehydrogenase deficiency (MCAD) as part of the newborn screening programme (normally when the baby is around 5 days old. However there are other more unusual FAOD, which are not routinely tested such as long-chain 3-hydroxyacyl coenzyme-A dehydrogenase deficiency (LCHAD) which is the main focus of this study.

    There is a small body of literature that suggests that during pregnancy, women who are carriers for FAOD such as LCHAD or those with an affected LCHAD fetus may be at risk of developing severe pregnancy-specific liver diseases such as acute fatty liver of pregnancy (AFLP) and HELLP syndrome (Haemolysis, elevated liver enzymes and low platelets) and this remains a concern.

    This study will prospectively determine the true incidence of FAOD (particularly LCHAD) in newborn babies from AFLP or HELLP pregnancies and assess the utility of acylcarnitine screening for LCHAD on routinely collected newborn screening blood spots. The common genetic mutation (E474Q) associated with LCHAD will also be analysed.

    In addition, the third trimester stresses may unmask women who are carriers for a FAOD leading to raised serum acylcarnitines using tandem mass spectrometry. Therefore, acylcarnitine levels in women with AFLP/HELLP will be compared to a cohort of women with low risk pregnancies undergoing routine antenatal care. It is possible that elevated levels of maternal acylcarnitines may identify an affected pregnancy thus raising earlier clinical suspicion of a FAOD defect.

  • REC name

    London - South East Research Ethics Committee

  • REC reference

    14/LO/0728

  • Date of REC Opinion

    7 Jul 2014

  • REC opinion

    Further Information Favourable Opinion