Occurrence and Gene Analysis of Primary Carnitine Deficiency in Li Nationality Newborns in Hainan Province

doi:10.12114/j.issn.1007-9572.2020.00.293

Abstract

Abstract: Background　Primary carnitine deficiency（PCD） is considered as a potentially lethal disease.The loss of carnitine transporter function will lead to the obstruction of fatty acid β oxidation metabolism.Without timely carnitine supplementation，patients with PCD will suffer from acute metabolic decompensation early in life，and bone disease and cardiomyopathy or even sudden death of arrhythmias will occur in the later stages of life.Therefore，PCD screening in neonatal period can prevent sudden death due to acute energy metabolism disorder or acute heart failure and ensure the quality of life and safety of life.Objective　To investigate the incidence of PCD in neonates of Li nationality in Hainan Province，and explore the types of gene mutations in Li nationality population.Methods　Through the Hainan Provincial Newborn Screening Network Platform，22 950 neonates（3 to 28 days after birth） of Li nationality born in Hainan Province from August 1 in 2016 to July 31 in 2019 were collected.The C0 and acylcarnitine（C2，C3，C16，and C18） were screened by tandem mass spectrometry.The suspected neonates（C0<10.0 μmol/L） and mothers were recalled for tandem mass spectrometry.Blood samples of those with low C0 were sent for SLC22A5 gene sequencing.The diagnosis of PCD was based on the detection of SLC22A5 gene mutation.Results　Among the initial screening of 22 950 neonates of Li nationality，the C0 of 14 cases was low，and the abnormal rate was1/1 639（14/22 950） with 7（1/1 710） males and 7（1/1 569） females.There was no significant difference in the abnormal rate of initial screening among Li neonates of different genders（χ2=0.026，P=0.872）.After SLC22A5 gene sequencing，10 neonates were diagnosed with PCD.The incidence of PCD in Li neonates was 1/2 295（10/22 950），of which seven cases had heterozygous mutations and three had homozygous mutations，and 5（1/2 394） cases were males and 5（1/2 196） were females.There was no significant difference in the incidence of PCD among Li neonates of different genders（χ2=0.019，P=0.892）.A total of eight types of gene mutations were detected，c.51C>G，c.760C>T，c.338G>A，c.428C>T，c.1340A>T，c.825G>A，c.4442C>T，and c.1400C>G.Conclusion　The incidence of PCD in Li neonates in Hainan Province is high（1/2 295）.PCD genes have abundant mutations，and c.51C>G and c.760C>T mutations are more common.

Key words: Deficiency diseases, Primary carnitine deficiency, Li nationality, Newborn screening, Tandem mass spectrometry, Genes

摘要： 背景　原发性肉碱缺乏症（PCD）被认为是一种潜在致死性疾病，肉碱转运蛋白功能缺陷会导致脂肪酸β氧化代谢受阻，如果没有及时补充肉碱，PCD患者在生命早期就会出现急性代谢失代偿，或晚期出现骨骼和心肌病或心律失常突然死亡。因此在新生儿期开展PCD筛查，对患儿早期治疗能防范急性能量代谢障碍危象或急性心力衰竭而猝死情况的发生，保证生活质量和生命安全。目的　调查海南省黎族新生儿PCD的发病情况，并探究黎族人群PCD基因突变类型。方法　借助海南省新生儿筛查网络平台，收集2016-08-01至2019-07-31在海南省出生的黎族新生儿22 950例（出生3~28 d）。通过串联质谱技术筛查黎族新生儿游离肉碱（C0）及酰基肉碱（C2、C3、C16、C18等指标）。可疑患儿（C0<10.0 μmol/L）需母婴同时召回，复查串联质谱检测，C0仍低者外送血标本进行SLC22A5基因测序。PCD基因确诊依据：检测到SLC22A5基因突变。结果　22 950例黎族新生儿初筛C0减低14例，初筛异常发生率为1/1 639（14/22 950），其中男7例（1/1 710），女7例（1/1 569）；不同性别黎族新生儿PCD初筛异常发生率比较，差异无统计学意义（χ2=0.026，P=0.872）。经SLC22A5基因测序，10例黎族新生儿确诊为PCD，黎族新生儿PCD发生率为1/2 295（10/22 950），其中7例为杂合突变，3例为纯合突变；男5例（1/2 394），女5例（1/2 196）；不同性别黎族新生儿PCD发生率比较，差异无统计学意义（χ2=0.019，P=0.892）。共检出8种基因突变类型：c.51C>G、c.760C>T、c.338G>A、c.428C>T、c.1340A>T、c.825G>A、c.4442C>T、c.1400C>G。结论　海南省黎族新生儿PCD发生率较高（1/2 295），基因突变类型较为丰富，以c.51C>G和c.760C>T基因突变较为常见。

关键词: 缺乏症, 原发性肉碱缺乏症, 黎族, 新生儿筛查, 串联质谱法, 基因

WEN Yingmei,ZHAO Zhendong,WANG Jie. Occurrence and Gene Analysis of Primary Carnitine Deficiency in Li Nationality Newborns in Hainan Province　[J]. Chinese General Practice, 2020, 23(18): 2299-2303. DOI: 10.12114/j.issn.1007-9572.2020.00.293.
温英梅,赵振东,王洁. 海南省黎族新生儿原发性肉碱缺乏症筛查及基因情况分析[J]. 中国全科医学, 2020, 23(18): 2299-2303. DOI: 10.12114/j.issn.1007-9572.2020.00.293.

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