Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing, P.R. China.
Newborn Screening Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing, China.
J Pediatr Endocrinol Metab. 2020 May 26;33(5):639-645. doi: 10.1515/jpem-2019-0420.
Background Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease. Methods The amino acids and acylcarnitines in dried blood spots were analyzed by TMS. Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Results Among the healthy newborns, 16 metabolic disorder cases were confirmed, giving a total birth prevalence of 1:3666 live births. Organic acidemia (OA) was the most common (9/16 patients; 56%), and methylmalonic acidemia was the most frequently observed OA (7/9 patients; 89%). Five infants were diagnosed with methylmalonic acidemia with homocystinuria type CblC, two with isolated methylmalonic acidemia, one with propionic acidemia, and one with isovaleric acidemia. Four patients (4/16, 25%) were diagnosed with hyperphenylalaninemia. One suffered with medium-chain acyl CoA dehydrogenase deficiency, one with carnitine uptake deficiency, and one with citrin deficiency. Eleven cases underwent genetic analysis. Seventeen mutations in eight IEM-associated genes were identified in 11 confirmed cases. Symptoms were already present within 2 days after birth in 44% (7/16) cases. The infant with propionic acidemia died at 7 days after birth. The other cases received timely diagnosis and treatment, and most of them grew well. Conclusions The results illustrate challenges encountered in disease management highlighting the importance of newborn screening for inherited metabolic disorders, which is not yet nationally available in our country. Regional newborn screening programs will provide a better estimation of the incidence of IEM.
个体先天性代谢缺陷（IEMs）是罕见疾病。串联质谱（TMS）扩展新生儿筛查是早期诊断的有效方法。在此，我们提供了该方法（2014 年 7 月至 2019 年 3 月）在识别北京有发生潜在致命疾病风险的新生儿中的应用的新生儿筛查程序。
采用 TMS 分析干血斑中的氨基酸和酰基肉碱。通过气相色谱-质谱、生化研究和基因分析对代谢物升高的新生儿进行确诊。
在健康新生儿中，共确诊了 16 例代谢障碍病例，总出生率为 1:3666 活产儿。有机酸血症（OA）最常见（16 例患者中有 9 例；56%），最常见的 OA 是甲基丙二酸血症（9 例中有 7 例；89%）。5 例婴儿被诊断为甲基丙二酸血症合并同型半胱氨酸尿症 CblC 型，2 例孤立性甲基丙二酸血症，1 例丙酸血症，1 例异戊酸血症。4 例（16 例中的 4 例；25%）被诊断为高苯丙氨酸血症。1 例患中链酰基辅酶 A 脱氢酶缺乏症，1 例患肉碱摄取缺陷症，1 例患 citrin 缺乏症。11 例患者进行了基因分析。在 11 例确诊病例中，8 个 IEM 相关基因的 17 个突变在 11 例中被发现。44%（7/16）的病例在出生后 2 天内出现症状。丙酸血症患儿在出生后 7 天死亡。其他病例得到了及时的诊断和治疗，大多数患儿生长良好。
结果说明了在疾病管理中遇到的挑战，突出了新生儿筛查遗传性代谢疾病的重要性，而我国尚未在全国范围内开展这一筛查。区域性新生儿筛查计划将更好地估计 IEM 的发病率。
