Objective To investigate the clinical diagnose,treatment and genetical features of infant and maternal primary carnitine deficiency (PCD) in newborn screening,so as to provide basis for clinical diagnosis and treatment of PCD. Methods Heel prick blood samples of newborns were collected on 3 days after birth for the genetic metabolic diseases screening by tandem mass spectrometry (MS/MS) in Zhejiang from January 1st 2009 to December 31st 2018.The infants with lower free carnitine(C0) and their mothers were recalled for diagnosis. Results A total of 4 459 infants were detected with lower C0 compared with the cut-off value (10 mol/L),and eventually 121 subjects were diagnosed with PCD (55 males and 66 females) in 3 040 815 newborns screening program.The prevalence rate was 1/25 131.The results of 111 PCD patients with complete follow-up data after diagnosis showed the initial screening C0 value was (5.94±2.01) mol/L,the recalled C0 value was (5.70±1.99)mol/L,and the difference was not significant (t=1.05,P>0.05).After treatment with L-carnitine,the C0 level at maintenance dose was (24.94±10.26) mol/L,which was significantly higher than that of pre-treatment (t=20.728,P＜0.001).A total of 64 maternal PCD were identified with a prevalence of 1/47 513 and an average C0 level of (3.31±1.79) mol/L.Furthermore,111 PCD patients had homozygous or compound heterozygous mutations by the genetic analysis of SLC22A5 gene.Consequently,a total of 42 cases were identified with SLC22A5 variants,of which c.1400C>G (p.S467C) was the most common mutation with the allelic frequency of 33.33%(74/222),followed by c.51C>G(p.F17L)with a frequency of 14.73%.There were 93.75% mothers undergoing genetic testing (60/64),and the SLC22A5 c.1400C>G (p.S467C) mutation accounted for 35.83% (43/120).Except for 2 deaths due to unknown reasons,other PCD children showed normal growth and development. Conclusionss PCD can be detected early by newborn screening and diagnosed by genetic analysis,but maternal carnitine deficiency should be excluded.SLC22A5 c.1400C>G (p.S467C) is the most common mutation in PCD patients in Zhejiang province.The treatment of L-carnitine is effective,but long-term treatment and follow-up are warranted.
Key words
primary carnitine deficiency /
maternal carnitine deficiency /
newborn genetic metabolic disease screening /
tandem mass spectrometry /
gene
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Lemonde H,Cleary M,Chakrapani A.Newborn screening for inborn errors of metabolism[J].Paediatrics & Child Health,2015,25(3):103-107.
[2] 赵正言.新生儿遗传代谢病筛查进展[J].中国实用儿科杂志,2014,29(8):586-589.
[3] Rasmussen J,Nielsen OW,Janzen N,et al .Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands[J].Inherit Metab Dis,2014,37:215-222.
[4] Gallant NM,Leydiker K,Wilnai Y,et al.Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California[J].Mol Genet Metab,2017,122(3):76-84.
[5] 韩连书,叶军,邱文娟,等.原发性肉碱缺乏症17例诊治与随访[J].中华儿科杂志,2012,50(6):405-409.
[6] 赵振东,王洁,谢曼芳,等.海南省少数民族自治市县原发性肉碱缺乏症筛查分析[J].中华检验医学杂志,2019,42(4):293-296.
[7] 中华人民共和国卫生部.新生儿疾病筛查管理办法[Z/OL].[2009-02-16].http://www.gov.cn/govweb/gongbao/content/2009/content_1371363.htm
[8] 杨茹莱,童凡,郑静.原发性肉碱缺乏症筛查诊断及治疗[J].中国实用儿科杂志,2019,34(1):14-18.
[9] 中华预防医学会出生缺陷预防与控制专业委员会新生儿遗传代谢病筛查学组.原发性肉碱缺乏症筛查与诊治共识[J].中华医学杂志,2019,99(2):88-92.
[10] El-Hattab AW,Scaglia F.Disorders of carnitine biosynthesis and transport[J].Mol Genet Metab,2015,116:107-112.
[11] Lee NC,Tang LS,Chien YH,et al.Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening[J].Mol Genet & Meta,2010,100(1):46-50.
[12] Han L,Wang F,Wang Y,et al.Analysis of genetic mutations in Chinese patients with systemic primary carnitine deficiency[J].Eur J Med Genet,2014,57:571-575.
[13] 郑静,张玉,洪芳,等.浙江省新生儿脂肪酸氧化代谢疾病筛查及随访分析[J].浙江大学学报:医学版,2017,46(3):248-255.
[14] Gallant NM,Leydiker K,Wilnai Y,et al.Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California[J].Mol Genet Metab,2017,122:76-84.
[15] Frigeni M,Balakrishnan B,Yin X,et al.Functional and molecular studies in primary carnitine deficiency[J].Human Mutation,2017,38(12):1684-1699.
[16] Roussel J,Labarthe F,Thireau J,et al.Carnitine deficiency induces a short QT syndrome[J].Heart Rhythm,2016,13:165-174.
[17] 马艳艳,杨艳玲.原发性肉碱缺乏症与心肌病[J].中国实用儿科杂志,2014,29(10):738-741.
[18] 郑宏,卢婷婷,李东晓,等.反复肺炎为主要表现的原发性肉碱缺乏症的临床特点[J].中华妇幼临床医学杂志,2016,12(5):553-557.
[19] El-Hattab AW,Li FY,Shen J,et al .Maternal systemic primary carnitine deficiency uncovered by newborn screening:clinical,biochemical,and molecular aspects[J].Genet Med,2010,12:19-24.
PDF(551 KB)
