淄博地区223 368例新生儿遗传代谢病串联质谱法筛查结果分析

牟凯; 许佳; 李雨雨; 李洪俞; 董丽萍; 刘娜

doi:10.7619/jcmp.20230648

淄博地区223 368例新生儿遗传代谢病串联质谱法筛查结果分析

Screening results of 223 368 cases of neonatal genetic metabolic diseases in Zibo by tandem mass spectrometry

摘要

摘要:
目的分析223 368例淄博地区新生儿遗传代谢病(IMD)串联质谱(MS/MS)法的筛查结果。
方法收集在山东省淄博市妇幼保健院进行IMD筛查的新生儿干血滤纸片223 368例, 均于出生后3~7 d采集足跟血，并使用MS/MS法进行IMD筛查。统计淄博地区新生儿IMD筛查阳性率; 分析淄博地区新生儿IMD发病类型及基因检测结果; 记录淄博地区IMD新生儿的随访结果。
结果确诊IMD患儿75例，发病率为0.034%(75/223 368)。其中，有机酸血症(OAD) 51例，占比最高(0.023%), 其次为氨基酸代谢病(AAD) 13例(0.006%)和脂肪酸氧化障碍(FAOD)11例(0.005%)。新生儿IMD中，以甲基丙二酸血症(MMA)、中链酰基辅酶A脱氢酶缺乏症(MCADD)发病率最高。其中OAD中，以MMA为主。AAD中，以高蛋氨酸血症、希特林蛋白缺乏症(NICCD)为主。FAOD中，以MCADD、原发性肉碱吸收障碍(PCD)为主。45例MMA新生儿中, 42例接受基因检测。其中40例检出MMACHC基因共22种突变位点，以c.609G>A(29.11%)、c.658_660delAAG(15.19%)、c.482G>A(12.66%)、c.80A>G(8.86%)为主; 2例检出MUT基因共4种突变位点。30例其他类型IMD新生儿中, 27例接受基因检测。其中6例MCADD中检出ACADM基因共8种突变位点，以c.387+1delG(29.11%)、c.449_452 del CTGA(15.19%)、c.1076C>T(12.66%)为主; 4例NICCD中检出 SLC25A13 基因共5种突变位点，以IVS16ins3kb(28.57%)、c.852_855del(28.57%)为主。随访期间, IMD患儿正常42例(56.00%), 发育迟缓31例(41.33%), 死亡2例(2.67%)。发育迟缓均为OAD, 分别为MMA 30例和丙酸血症1例。
结论淄博地区新生儿IMD发病率为0.034%, 以OAD为主，其中MMA发病率最高，并以MMACHC基因变异为主。

Abstract:
Objective To analyze the results of tandem mass spectrometry (MS/MS) screening of 223 368 neonates with inherited metabolic diseases (IMD) in Zibo.
Methods A total of 223 368 cases of dry blood filter paper were collected from Zibo Maternal and Child Health Care Hospital of Shandong Province for IMD screening, and heel blood was collected at 3 to 7 days after birth for IMD screening by MS/MS method. The positive rate of newborn IMD screening in Zibo was analyzed; the incidence types and gene detection results of neonatal IMD in Zibo were analyzed; the follow-up results of IMD neonates in Zibo were recorded.
Results A total of 75 neonates were diagnosed as IMD, with an incidence of 0.034% (75/223 368). Among them, 51 cases of organic acid disorder (OAD) accounted for the highest proportion (0.023%), followed by 13 cases of amino acid disorder (AAD) (0.006%) and 11 cases of fatty acid oxidation disorders (FAOD) (0.005%). Methylmalonic acidemia (MMA) and medium chain acyl coenzyme A dehydrogenase deficiency (MCADD) were the most common IMDs in neonates. In OAD, MMA was the main component. In AAD, hypermethioninemia and Hitlin protein deficiency (NICCD) were the main symptoms. In FAOD, MCADD and primary carnitine absorption disorder (PCD) were the main cases. During the follow-up, 42 cases (56.00%) were normal, 31 cases (41.33%) were stunted, and 2 cases (2.67%) died. Of the 45 MMA newborns, 42 underwent genetic testing. A total of 22 MMACHC gene mutation sites were detected in 40 cases, mainly c.609G >A (29.11%), c.658_ 660delAAG (15.19%), c.482G>A (12.66%), c.80A>G (8.86%). A total of 4 mutational sites of MUT gene were detected in 2 cases. Of the 30 newborns with other types of IMD, 27 underwent genetic testing. A total of 8 ACADM gene mutation sites were detected in 6 cases of MCADD, mainly c.387+1delG (29.11%), c.449_452 del CTGA (15.19%), and c.1076C>T (12.66%); a total of 5 SLC25A13 gene mutation sites were detected in 4 NICCD, mainly IVS16ins3kb (28.57%) and c.852_855 del (28.57%). All developmental delays were OAD, including 30 cases of MMA and 1 case of propionic acidemia.
Conclusion The incidence rate of neonatal IMD in Zibo area is 0.034%, most of neonates suffer OAD, among which the incidence rate of MMA is the highest, and MMACHC gene mutation is the main mutation.

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