Carling Rachel S, Hedgethorne Katy, Chakrapani Anupam, Hall Patricia L, Flynn Nick, Greenfield Toby, Moat Stuart J, Ssali Joshua, Shakespeare Lynette, Taj Nazia, Wu Teresa H Y, Anderson Mark, Ghosh Arunabha, Lemonde Hugh, Pierre Germaine, Sharrard Mark, Sreekantam Sreevidya, Bonham James R
Biochemical Sciences, Synnovis, Guys & St Thomas' NHSFT, London SE1 7EH, UK.
GKT School of Medical Education, Kings College London, London WC2R 2LS, UK.
Int J Neonatal Screen. 2024 Mar 13;10(1):24. doi: 10.3390/ijns10010024.
Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0-9.6) and 4.0 (1.8->70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in 'asymptomatic' individuals ( = 17), demonstrating a median (range) C5C of 3.0 (1.8-7.1) whilst 'clinically affected' patients ( = 7), showed a median (range) C5C of 13.9 (7.7-70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.
自英国于2015年开始对异戊酸血症进行新生儿筛查以来，处方的变化增加了因新戊酰肉碱导致的假阳性（FP）结果的发生率。对2015年至2022年期间的筛查结果进行回顾，确定了24例真阳性（TP）和84例假阳性病例，其中76/84例确认存在新戊酸盐干扰。初始C5肉碱（C5C）无法区分FP和TP，其C5C中位数（范围）分别为2.9（2.0 - 9.6）和4.0（1.8 ->70）µmol/L，通过协作实验室综合报告（CLIR）进行的精准新生儿筛查也无法区分，该方法仅识别出1/47例假阳性病例。然而，在TP病例中，疾病严重程度与“无症状”个体（n = 17）的初始C5C呈相关性，其C5C中位数（范围）为3.0（1.8 - 7.1）µmol/L，而“临床受累”患者（n = 7）的C5C中位数（范围）为13.9（7.7 - 70）µmol/L。这些发现使得在筛查算法中引入双重临界值以降低FP发生率成为可能，初始C5C结果≥5 µmol/L会触发紧急转诊，而结果>2.0且<5.0 µmol/L则会促使进行二级C5 - 等压线检测。这将避免对处于特定风险的婴儿延迟转诊，同时降低其余婴儿的FP率。
