Objective: To study the gene mutation profile of primary carnitine deficiency (PCD) in neonates, and to provide a theoretical basis for early diagnosis and treatment, genetic counseling, and prenatal diagnosis of PCD.
Methods: Acylcarnitine profile analysis was performed by tandem mass spectrometry using 34 167 dry blood spots on filter paper. The SLC22A5 gene was sequenced and analyzed in neonates with free carnitine (C0) levels lower than 10 μmol/L as well as their parents.
Results: In the acylcarnitine profile analysis, a C0 level lower than 10 μmol/L was found in 10 neonates, but C0 level was not reduced in their mothers. The 10 neonates had 10 types of mutations at 20 different sites in the SLC22A5 gene, which included 4 previously unreported mutations: c.976C>T, c.919delG, c.517delC, and c.338G>A. Bioinformatics analysis showed that the four new mutations were associated with a risk of high pathogenicity.
Conclusions: Tandem mass spectrometry combined with SLC22A5 gene sequencing may be useful for the early diagnosis of PCD. Identification of new mutations enriches the SLC22A5 gene mutation profile.
目的: 对新生儿原发性肉碱缺乏症（PCD）基因突变谱进行分析，为PCD早期诊断和治疗以及遗传咨询和产前诊断提供理论依据。
方法: 对进行新生儿串联质谱筛查的34 167份滤纸干血片进行血酰基肉碱谱分析，对其中游离肉碱（C0）低于10 μmol/L的新生儿及父母行SLC22A5基因测序。
结果: 酰基肉碱谱筛查C0低于10 μmol/L的新生儿10例，患儿母亲游离肉碱均未见降低，10例患儿的SLC22A5基因测序检测到10种20个突变位点，其中c.976C > T、c.919delG、c.517delC、c.338G > A未见报道，生物信息学分析提示高致病风险。
结论: 串联质谱技术结合SLC22A5基因测序有助于PCD早期诊断，新突变的发现丰富了SLC22A5基因突变谱。