【摘要】 目的:原发性肉碱缺乏症（primary carnitine deficiency,PCD）是一种罕见的可致新生儿死亡的脂肪酸代谢紊乱性疾病。本研究对新生儿足跟血行串联质谱分析筛查出的肉碱缺乏儿,进一步行血肉碱水平分析及SLC22A5基因检测,为PCD的早期诊断提供依据,同时探索血肉碱水平与SLC22A5基因型的关系。方法:收集新生儿血串联质谱筛查游离肉碱（free carnitine,C0）值<10μmol/L的40例患儿为研究对象,用Sanger测序方法对PCD的致病基因SLC22A5基因进行检测,分析肉碱水平、基因检测结果及两者的关系。结果:共检出SLC22A5基因变异15种（42个）,包括11种致病或可能致病变异和4种意义不明变异。发现c.288del G（p.G96fs X33）,c.744₇45ins TCG（p.M258_L259ins S）,c.752A>G（p.Y251C）,c.495C>A（p.R165E）,c.1298T>C（p.M433T）5种新突变。在40例串联质谱初筛肉碱缺乏的患儿中,14例被确诊为PCD,包括SLC22A5基因纯合突变2例,复合杂合突变12例;14例检出1个SLC22A5基因突变;12例未检出SLC22A5基因突变。确诊为PCD的患儿初筛C0值为（4.95±1.62）μmol/L,复查C0值为（3.90±1.33）μmol/L;未检出突变的患儿初筛C0值为（7.04±2.05）μmol/L,复查C0值为（8.02±2.87）μmol/L,确诊为PCD的患儿与未检出突变患儿的初筛及复查C0值差异均有统计学意义（均P<0.05）;检出截短突变的患儿与未检出截短突变的患儿初筛C0值差异有统计学意义（P=0.022）。结论:发现的5种新突变丰富了SLC22A5基因突变谱;新生儿足跟血串联质谱初筛C0值<5μmol/L与SLC22A5基因纯合或复合杂合突变型具有更强的相关性;具有截短突变的患儿较不含截短突变患儿的C0值可能更低。更多还原

【Abstract】 Objective: Primary carnitine deficiency（PCD） is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22 A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD,and to explore the relationship between carnitine in blood and SLC22 A5 genotype.Methods: A total of 40 neonates with low free carnitine（C0<10 μmol/L） in blood were the subjects of the study. SLC22 A5 gene was detected by Sanger sequencing to analyze the value of carnitine, the results of gene test and their relationship.Results: A total of 15 variants of SLC22 A5 gene were detected, including 11 pathogenic or likely pathogenic variants and 4 variants of uncertain significance. There were 5 new mutations: c.288 del G（p.G96 fs X33）, c.744₇45 ins TCG（p.M258_L259 ins S）, c.752 A>G（p.Y251 C）, c. 495 C>A（p. R165 E）, and c. 1298 T>C（p. M433 T）. We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation,and 12 with no mutation among 40 children. The C0 concentration of children with SLC22 A5 gene homozygous or complex heterozygous mutations was（4.95±1.62） μmol/L in the initial screening, and（3.90±1.33） μmol/L in the second screening. The C0 concentration of children with no mutation was（7.04±2.05） μmol/L in the initial screening,and（8.02±2.87） μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening（both P<0.05）, as well as between children with truncated mutation and with untruncated mutation in C0 concentration of the initial screening（P=0.022）.Conclusion: There are 5 new mutations which enriched the mutation spectrum of SLC22 A5 gene. C0<5 μmol/L is highly correlated with SLC22 A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.更多还原