374. Using acylcarnitine screening for identification of newborn fatty acid oxidation disorders (FAOD) from pregnancies complicated by acute fatty liver

Abstract

Introduction Acute fatty liver of pregnancy (AFLP) is a rare but potentially fatal disease developing in the third trimester and affects 5 per 100,000 pregnancies. Women at risk include primips, those with BMI 20 and twin pregnancies.1 The underlying pathophysiology in AFLP is poorly understood but has been linked with newborn FAOD with long-chain 3-hydroxyacyl coenzyme-A dehydrogenase deficiency (LCHAD) reported in 1 in 5 babies.2 Since defective LCHAD enzyme activity leads to accumulation of acylcarnitines species of varying carbon length in the blood, acylcarnitine screening in babies born from AFLP pregnancies may help to pick up cases non-invasively. Aims We set up the S creening of A cylcarnitines of M others and B abies in A FLP (SAMBA) to: Assess whether acylcarnitine screening from routinely collected national screening programme newborn blood spots is a reliable method to identify FAOD. Prospectively define the incidence of LCHAD in AFLP pregnancies. Methods AFLP was diagnosed using the Swansea criteria.[c] Tandem Mass Spectrometry (MS) API5000 was used to measure free carnitine (C0) and acylcarnitines[C2,C3,C4,C5,C8,C10,C14,C14:1, C16,C16OH,C16:1OH,C18OH,C3DC(DC = dicarboxylic),C4DC (C5OH & methylmalonyl carnitine-isobaric), C5DC(glutaryl) and C6DC] from the newborn screening blood spot cards. DNA analysis was undertaken in stillbirth cases to identify the E474Q mutation reported in 87% of LCHAD cases. Results Between 2012-current, 12 women were diagnosed with AFLP and patients presented with nausea, vomiting, headache, malaise and jaundice. 16.6% were twin pregnancies. In 13/14 babies, all measurable hydroxyacylcarnitines (free, short, medium and long-chain) were found to be normal. There was 1 stillbirth (perinatal mortality rate 71.4 per 1000) and DNA analysis was negative for the E474Q mutation. Conclusions The application of tandem mass spectrometry has proved to be an effective and non-invasive tool to identify most FAOD. However, in our cohort so far, we have been unable to demonstrate any indication of newborn LCHAD or other FAOD in AFLP cases.