目的 研究血3-羟基异戊酰肉碱（C5OH）增高对诊断相关遗传代谢病（IMD）的意义，并探讨北方人群中该指标异常患儿的疾病谱及遗传学特点。方法 回顾性分析2012年11月至2021年10月住院患儿的IMD筛查诊断资料，包括干血斑串联质谱（MS/MS）、尿液气相质谱（GC-MS）检测以及基因变异的高通量测序结果。分析C5OH指标异常患儿的血、尿代谢谱及基因变异谱。结果 53 119例0~7岁住院患儿检出C5OH增高48例（0.090%），结合尿GC-MS分析生化诊断相关IMD 9例（0.017%），且均基因验证。提示多种羧化酶缺乏（MCD）的4例患儿中，2例检出HLCS变异，确诊为全羧化酶合成酶缺乏；2例检出BTD变异，确诊为生物素酶缺乏。提示β-酮硫解酶缺乏症的2例均检出ACAT1变异；提示3羟基3甲基戊二酸尿症的1例检出HMGCL变异。生化诊断未分型疑似MCD或3-甲基巴豆酰辅酶A羧化酶缺乏的2例，1例检出HLCS变异，另1例检出BTD变异，最终确诊MCD。C5OH单一指标假阳性率0.073%，阳性预测值18.75%；合并多指标（C4OH、C3、C5:1）假阳性率0.009%，阳性预测值58.33%；合并尿GC-MS分析无一假阳性，阳性预测值达100%。结论 MCD 是血C5OH增高患儿中的主要疾病类型。对于C5OH相关IMD，MS/MS联合GC-MS的代谢分析具有较高的诊断效率及提前指导干预的临床价值。

Objective To investigate the significance of elevated blood 3-hydroxyisovalerylcarnitine (C5OH) in the diagnosis of inherited metabolic diseases (IMD) and to explore the disease spectrum and genetic characteristics of children with abnormal C5OH in the population of northern China. Methods The data of IMD screening and diagnosis in hospitalized children from November 2012 to October 2021 were retrospectively analyzed, including tandem mass spectrometry (MS/MS) screening of blood metabolites, gas chromatography-mass spectrometry (GC-MS) analysis of urine metabolites and high-throughput sequencing analysis of gene variations. The blood and urine metabolic spectrum and gene variation spectrum of children with abnormal C5OH were analyzed. Results Among 53119 hospitalized children aged 0 to 7 years who underwent MS/MS screening for IMD, 48 (0.090%) children with increased C5OH were detected. Combined with urine GC-MS analysis, 9 (0.017%) children obtained biochemical diagnosis of IMD which verified by gene analysis. Of the 4 children with multiple carboxylase deficiency (MCD), 2 had HLCS gene variation and were confirmed as holocarboxylase synthetase deficiency, while the other 2 had BTD gene variation and were confirmed as biotinidase deficiency. ACAT1 variation was detected in 2 children with β-ketothiolase deficiency, and HMGCL variation was detected in 1 child with 3-hydroxy-3-methyl-glutaricacidemia. In 2 children with suspected MCD or 3-methylcrotonyl coenzyme A carboxylase deficiency that were not classified by biochemical diagnosis, HLCS variation was detected in 1 child, and BTD variation was detected in the other child, and MCD was finally diagnosed. The false positive rate of C5OH detection was 0.073% and the positive predictive value was 18.75%. The false positive rate of C5OH combined with other indicators (C4OH, C3 and C5:1) was 0.009%, and the positive predictive value was 58.33%. There was no false positive in the analysis of C5OH combined with urinary GC-MS, and the positive predictive value was 100%. Conclusions MCD is the main disease type in children with increased C5OH. For C5OH-related IMD, MS/MS combined with GC-MS metabolic analysis has high diagnostic efficiency and clinical value of guiding intervention in advance.