探讨海南省新生儿多种遗传代谢病(IEM)的发病情况。

选择2024年1月1日至12月31日在海南省出生、监护人同意进行新生儿IEM筛查的86 543例新生儿为研究对象。采用串联质谱技术，对新生儿足跟血滤纸干血斑标本进行多种IEM初筛、复筛。对复筛结果呈阳性的部分新生儿，采集外周血，基于全外显子组测序(WES)技术，确诊IEM种类和基因突变情况。采用χ²检验，对不同性别、出生胎龄及体重、民族、户籍所在地新生儿的IEM初筛阳性率进行统计学比较，进一步采用χ²分割法进行两两比较，并采用Bonferroni法调整检验水准后进行统计学分析。本研究遵循的程序符合海南省妇女儿童医学中心伦理委员会标准，并通过该伦理委员会审批(审批文号：HNWCMC伦审2026年第151号)。

①2024年，海南省活产新生儿为92 170例，对其中86 543例进行IEM筛查，IEM筛查率为93.89%。这86 543例新生儿的IEM初筛阳性率为3.58%(3 094/86 543)。对初筛结果呈阳性中的2 591例进行IEM复筛，IEM复筛阳性率为9.46%(245/2 591)，对复筛结果呈阳性中的136例(55.51%，136/245)新生儿进行基因检测后，最终被确诊的IEM患儿为38例，海南省新生儿的IEM发病率约为4.39×10^－4(38/86 543)。②出生胎龄<37周新生儿IEM初筛阳性率高于出生胎龄≥37~42周者，并且差异有统计学意义(χ²＝361.64，P<0.001)。不同出生体重新生儿的IEM初筛阳性率总体比较，差异亦有统计学意义(χ²＝291.65，P<0.001)，进一步对出生体重<2 500 g、≥2 500~4 000 g与>4 000 g新生儿的IEM初筛阳性率进行任意两两比较，差异均有统计学意义(P≤0.001)。不同民族新生儿的IEM初筛阳性率总体比较，差异有统计学意义(χ²＝36.12，P<0.001)，进一步进行两两比较的结果显示，黎族新生儿的IEM初筛阳性率高于汉族和苗族，并且差异均有统计学意义(P<0.001、P＝0.006)。不同户籍所在地新生儿IEM初筛阳性率比较，差异有统计学意义(χ²＝80.62，P<0.001)，进一步进行两两比较的结果显示，户籍所在地为海南省少数民族市、县新生儿的IEM初筛阳性率高于汉族市、县，并且差异有统计学意义(P<0.001)。③本研究86 543例新生儿中，IEM相关基因突变检出率为7.16×10^－4(62/86 543)，检出的前4位突变基因为SLC22A5、SLC25A13、ACADS和ASS1，检出前3位基因突变位点分别为c.51C>G、c.852_855del、c.322G>A。④经基因检测确诊的38例IEM新生儿中，氨基酸代谢病为4例、有机酸血症为7例、尿素循环障碍为5例、脂肪酸氧化代谢障碍为22例。新生儿IEM筛查确诊数量最高的3种IEM依次为原发性肉碱缺乏症(13例)、短链酰基辅酶A脱氢酶缺乏症(6例)、瓜氨酸血症Ⅱ型(5例)。

海南省新生儿的IEM发病率较高、种类较多。建议海南省对新生儿开展多种IEM筛查，并加强IEM筛查呈阳性患儿的管理。

To explore the incidence of various inborn errors of metabolism (IEM) in newborns in Hainan Province.

A total of 86 543 newborns born in Hainan Province from January 1 to December 31, 2024, whose guardians agreed to undergo neonatal IEM screening, were selected as the study subjects. Using tandem mass spectrometry detection technology, initial and re-screening of various IEM were conducted on dried blood spot specimens collected from the heels of newborn infants. For some newborns who tested positive in the rescreening, peripheral blood was collected, and the type of IEM and gene mutations were confirmed by whole exome sequencing (WES) detection technology. The positive rates of initial IEM screening among newborns of different genders, gestational ages, birth weights, ethnicities, and registered residences were compared by chi-square test, and further pairwise comparisons were performed using the chi-square splitting method, and the Bonferroni method was used to adjust the significance level. This study was conducted in accordance with the ethical standards of Hainan Women and Children′s Medical Center, and was approved by its Ethics Committee (Approval No.HNWCMC-2026-151).

①In 2024, there were 92 170 live births in Hainan Province, and 86 543 of them underwent IEM screening, with an IEM screening rate of 93.89%. Among these 86 543 newborns, the positive rate of initial IEM screening was 3.58% (3 094/86 543). And 2 591 cases underwent IEM rescreening, with an IEM rescreening rate of 83.74% (2 591/3 094). Among them, 245 cases were positive for IEM rescreening, the positive rate of IEM rescreening was 9.46% (245/2 591), and 136 (55.51%, 136/245) newborns underwent genetic testing, and 38 were finally diagnosed with IEM. The incidence rate of IEM in newborns was about 4.39×10^-4 (38/86 543). ②The positive rate of initial IEM screening in newborns with gestational age <37 weeks was higher than that in newborns with gestational age ≥37 to 42 weeks, and the difference was statistically significant (χ²=361.64, P<0.001). The overall comparison of the positive rate of initial IEM screening among newborns with different birth weights also showed a statistically significant difference (χ²=291.65, P<0.001). Further pairwise comparisons revealed that the positive rate of initial IEM screening in newborns with birth weight <2 500 g, ≥2 500 to 4 000 g, and >4 000 g differed significantly in any pairwise comparison (P≤0.001). The overall comparison of the positive rate of initial IEM screening among newborns of different ethnic groups showed a statistically significant difference (χ²=36.12, P<0.001). Further pairwise comparisons revealed that the positive rate of initial IEM screening in Li ethnic group newborns was higher than that in Han and Miao ethnic group newborns, and both the differences were statistically significant (P<0.001, P=0.006). The comparison of the positive rate of initial IEM screening among newborns with different registered residence also showed a statistically significant difference (χ²=80.62, P<0.001). Further pairwise comparisons revealed that the positive rate of initial IEM screening in newborns from ethnic minority cities and counties in Hainan Province was higher than that in newborns from Han ethnic group cities and counties in Hainan Province, and the difference was statistically significant (P<0.001). ③Among the 86 543 newborns, the detection rate of IEM-related gene mutation was 7.16×10^-4 (62/86 543). The top four detected gene mutations were SLC22A5, SLC25A13, ACADS, and ASS1 gene mutations. The top three detected gene mutation sites were c. 51C>G, c. 852_855del, and c.322G>A, respectively. ④Among the 38 newborns with IEM confirmed by genetic testing, 4 cases were amino acid metabolism disorders, 7 cases were organic acidemia, 5 cases were urea cycle disorders, and 22 cases were fatty acid oxidation metabolism disorders. The top three IEM diseases in terms of confirmed cases were primary carnitine deficiency (13 cases), short-chain acyl-CoA dehydrogenase deficiency (6 cases), and citrullinemia type Ⅱ (5 cases).

The incidence of IEM among newborns in Hainan Province is relatively high, with a diverse range of types. It is recommended to initiate early screening for various IEM in newborns and to enhance the management of infants with positive IEM screening results in Hainan Province.