目的 了解本市应用串联质谱技术对新生儿甲基丙二酸血症(MMA)进行筛查的相关指标浓度值分布特征,评估3-羟基十六烯酰基肉碱(C16:1-OH)指标在MMA疾病判读中的应用价值,为提高MMA筛查阳性预测值及筛查效率提供依据。方法 利用串联质谱技术对2013年10月-2019年7月当地出生的185 239例新生儿进行MMA筛查。比较不同性别、孕周和出生体重分组下,MMA疾病相关指标水平;比较确诊样本的初筛和复查指标水平。结果 确诊44例患儿,单纯型5例,合并型39例,总体患病率约为0.023 7%(44/185 239);不同性别、孕周和出生体重分组下,游离肉碱(C0)、丙酰基肉碱(C3)、丙酰基肉碱/游离肉碱(C3/C0)、丙酰基肉碱/乙酰基肉碱(C3/C2)、C16:1-OH和蛋氨酸(MET)等指标浓度值分布差异均有统计学意义(P＜0.001)。确诊样本的初筛和复查结果比较,复查样本中的C3/C2水平高于初筛样本(Z=5.10, P＜0.001),而复查样本中C16:1-OH水平低于初筛样本(Z=5.236, P＜0.001)。C16:1-OH指标诊断MMA的ROC曲线下面积为0.951(95%CI:0.914~0.987),权重指数约为15.46。结论 在MMA新生儿筛查工作中,根据采血时间、出生体重及胎龄综合判读,可降低初筛阳性率;C16:1-OH指标可协助初筛样本(自出生3~7 d采血)MMA疾病的判读,提高阳性预测值,能有效提高筛查效率,早诊断、早治疗,降低病残率。

Objective To understand distribution characteristics of the concentration of relevant indicators in neonatal methylmalonic academia (MMA) screening by tandem mass spectrometry technology, and to evaluate the application value of 3-hydroxyhexadecenoyl carnitine (C16:1-OH) in the interpretation of MMA diseases, so as to provide basis for improving the positive predictive value of MMA screening and screening efficiency. Methods A total of 185 239 local newborns born between October 2013 and July 2019 were conducted MMA screening using tandem mass spectrometry technology.The levels of MMA disease-related indicators were compared among children in different gender, gestational age and birth weight groups.The initial screening levels were compared with re-examination indicator levels of confirmed samples. Results A total of 44 cases were diagnosed, 5 cases with simple type, 39 cases with combined type, and the overall prevalence was about 0.023 7%(44/185 239).Grouped by gender, gestational age and birth weight, free carnitine (C0), propionyl carnitine (C3), propionyl carnitine/free carnitine (C3/C0), propionyl carnitine/acetyl carnitine (C3/C2), C16:1-OH and methionine (MET) and other index concentration value distribution differences were statistically significant (P＜0.001).Compared with the results of initial screening, the level of C3/C2 in the re-examination samples was significantly higher (Z=5.10,P＜0.001), while the C16:1-OH level in the re-examination samples was significantly lower (Z=5.236, P＜0.001).The area under the ROC curve of the C16:1-OH indicator was 0.951 (95%CI: 0.914 - 0.987), and the weight index was approximately 15.46. Conclusions When screening MMA in neonates, medical staff are suggested give comprehensive interpretation based on the time of blood collection, birth weight and gestational age so as to reduce the positive rate of initial screening.The C16:1-OH indicator is helpful in the interpretation of MMA disease in the primary screening sample (blood sampling from 3 to 7 days after birth), and can effectively improve the positive predictive value and screening efficiency, thereby achieving early diagnosis, early treatment, and reducing the rate of disability.