National Metabolic Service, Starship Children's Hospital, P.O. Box 92024, Auckland 1142, New Zealand.
Newborn Metabolic Screening Unit, Auckland City Hospital, Auckland, New Zealand.
J Inherit Metab Dis. 2019 Jan;42(1):86-92. doi: 10.1002/jimd.12030.
When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen-positive if they had initial and repeat free carnitine (C0) levels of less than 5.0 μmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. A review of the literature suggests that these nine women reflect less than half the true prevalence and that CUD is relatively common. However, the NZ results (two infants) suggest a very low sensitivity and positive predictive value of NBS. While patients presenting with significant disease due to CUD are well described, the majority of adults with CUD are asymptomatic. Nonetheless, treatment with high-dose oral L-carnitine is recommended. Compliance with oral L-carnitine is likely to be poor long term. This may represent a specific risk as treatment could repress the usual compensatory mechanisms seen in CUD, such that a sudden discontinuation of treatment may be dangerous. L-carnitine is metabolized to trimethylamine-N-oxide (TMAO) and treated patients have extremely high plasma TMAO levels. TMAO is an independent risk factor for atherosclerosis and, thus, caution should be exercised regarding long-term treatment with high-dose carnitine of asymptomatic patients who may have a biochemical profile without disease. Due to these concerns, the NZ Newborn Metabolic Screening Programme (NMSP) initiated a review via a series of advisory and governance committees and decided to discontinue screening for CUD.
在对肉碱摄取障碍（CUD）进行筛查时，如果新西兰（NZ）新生儿筛查（NBS）服务的初始和重复游离肉碱（C0）水平低于 5.0 μmol/L，则将婴儿视为筛查阳性。自 2006 年以来，NBS 服务已发现 2 名婴儿具有与新生儿 CUD 一致的生化和遗传特征，以及 9 名具有与母体 CUD 一致特征的母亲。对文献的回顾表明，这 9 名女性反映的真实患病率不到一半，而且 CUD 相对常见。然而，NZ 的结果（2 名婴儿）表明 NBS 的敏感性和阳性预测值非常低。虽然由于 CUD 而导致严重疾病的患者已有详细描述，但大多数 CUD 成年人无症状。尽管如此，仍建议使用大剂量口服左旋肉碱进行治疗。长期来看，口服左旋肉碱的依从性可能很差。这可能是一个特定的风险，因为治疗可能会抑制 CUD 中常见的代偿机制，以至于突然停止治疗可能会很危险。左旋肉碱代谢为三甲胺-N-氧化物（TMAO），接受治疗的患者的血浆 TMAO 水平极高。TMAO 是动脉粥样硬化的独立危险因素，因此，对于无症状且可能具有生化特征但无疾病的患者，应谨慎考虑长期使用大剂量肉碱进行治疗。由于这些担忧，NZ 新生儿代谢筛查计划（NMSP）通过一系列咨询和治理委员会启动了一项审查，并决定停止对 CUD 的筛查。
