新生儿原发性肉碱缺乏症诊治与基因突变分析

目的 分析青岛地区新生儿原发性肉碱缺乏症患儿的SLC22A5基因突变特点,探讨原发性肉碱缺乏症的诊断和治疗。方法 2015年1月-2018年8月对278 180例新生儿利用串联质谱技术检测游离肉碱及酰基肉碱,并且利用肉碱转运蛋白基因突变检测对游离肉碱降低的患儿进行确诊。结果 共确诊5例原发性肉碱缺乏症患儿,发病率0.001 8%(1/55 636)。对确诊患儿给予左旋肉碱治疗,100~300 mg/(kg·d),分3次口服,随访治疗1个月后,血游离肉碱均升至正常。5例患儿均检测到基因突变。其中1例患儿为纯合突变,为c.1400C>G(p.S467C)/ c.1400C>G(p.S467C),其它4例为复合杂合突变,分别为:c.1400C>G(p.S467C)/c.1433C>T(p.P478L);c.1400C>G(p.S467C)/c.760C>T(p.R254X);c.1400C>G(p.S467C)/c.428C>T(p.P143L);c.1400C>G(p.S467C)/c.393+1G>A(错误剪接)。结论 c.1 400C>G(p.S467C)为青岛地区新生儿原发性肉碱缺乏症患儿SLC22A5基因主要突变(60%)类型,基因检测分析有助于原发性肉碱缺乏症的诊断。左旋肉碱治疗效果好,预后良好。

Analysis on the diagnosis,treatment and gene mutation of neonatal primary carnitine deficiency

Objective To investigate the mutation characteristics of SLC22A5 gene of neonatal primary carnitine deficiency(PCD) in Qingdao area,and to discuss the diagnosis and treatment of PCD.Methods The free carnitine(C0) and acylcarnitine levels in the blood of 278 180 neonates from newborns screening program in Qingdao were measured by tandem mass spectrometry from January 2015 to August 2018.The mutations of carnitine transporter protein were tested in children with low C0 level and the diagnosis was made. Results A total of 5 cases were diagnosed with PCD,with the incidence rate of 0.001 8%(1/55 636).PCD Children were treated with 100-300 mg/(kg·d) of carnitine,and were followed up for 1 month till the blood free carnitine rose to normal.Five child were detected with gene mutations,and one children was homozygous mutation of c.1400C>G(p.S467C)/ c.1400C>G(p.S467C).The compound heterozygous mutations in four cases included c.1400C>G(p.S467C)/c.1433C>T(p.P478L); c.1400C>G(p.S467C)/c.760C>T(p.R254X); c.1400C>G(p.S467C)/c.428C>T(p.P143L); c.1400C>G(p.S467C)/c.393+1G>A (error splicing). Conclusions c.1400C>G(p.S467C) is the major mutation(60%) in SLC22A5 gene of PCD children in Qingdao area.Genetic analysis is helpful for the diagnosis of PCD.And carnitine is effective in the treatment of PCD and will promote better prognosis of PCD children.