六例肉碱棕榈酰基转移酶2缺乏症患儿临床特征及基因变异分析
Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency
张彦 1邱文娟 2张惠文 2陈婷 2徐烽 2顾学范 2韩连书2
作者信息
- 1. 杭州市儿童医院内分泌科,浙江 杭州 310005
- 2. 上海交通大学附属新华医院 上海市儿科医学研究所小儿内分泌遗传代谢科,上海 200092
- 折叠
摘要
目的:探讨肉碱棕榈酰基转移酶2(CPT2)缺乏症患儿的临床表型及基因变异特点.方法:回顾性分析6例CPT2缺乏症患儿的临床和基因检测资料,采用串联质谱法检测血酰基肉碱水平,全外显子基因测序法检测基因变异.结果:6例CPT2缺乏症患儿中男性4例、女性2例,平均确诊年龄为32个月(15 d～9岁).其中1例无临床症状及实验室检查异常、2例迟发型、3例婴儿型.3例由新生儿筛查确诊;3例因临床表现就诊,起病时有发热、肌肉乏力伴肌酶增高.5例患儿表现为游离肉碱降低,棕榈酰基肉碱、十八碳烯酰肉碱升高.6例患儿检测到CPT2基因变异8个位点(携带双位点突变4例,携带单位点突变2例),3种为已知变异(p.R631C、p.T589M和p.D255G),5种为新报道变异(p.F352L、p.R498L、p.F434S、p.A515P、c.153-2A>G).经PolyPhen2和SIFT软件预测,5个新报道变异中c.153-2A>G和p.F352L为疑似致病变异,p.R498L、p.F434S和p.A515P为临床意义未明变异.结论:CPT2缺乏症临床表型多样,通过新生儿血串联质谱筛查及基因检测有助于早期诊断,确诊后及时治疗大多预后良好.
Abstract
Objective:To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2(CPT2)deficiency.Methods:The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed.The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing,respectively.Results:There were 4 males and 2 females with a mean age of 32 months(15 d-9 years)at diagnosis.One case was asymptomatic and with normal laboratory test results,2 had delayed onset,and 3 were of infantile type.Three cases were diagnosed at neonatal screening,and 3 cases presented with clinical manifestations of fever,muscle weakness,and increased muscle enzymes.Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines.CPT2 gene variants were detected at 8 loci in 6 children(4 harboring biallelic mutations and 2 harboring single locus mutations),including 3 known variants(p.R631C,p.T589M,and p.D255G)and 5 newly reported variants(p.F352L,p.R498L,p.F434S,p.A515P,and c.153-2A>G).It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants,while p.R498L,p.F434S and p.A515P were variants of unknown clinical significance.Conclusions:The clinical phenotypes of CPT2 deficiency are diverse.An early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing,and most patients have good prognosis after a timely diagnosis and treatment.
关键词
肉碱棕榈酰基转移酶2缺乏症/临床特征/CPT2基因/串联质谱技术/游离肉碱/病例报告Key words
Carnitine palmitoyltransferase 2 deficiency/Clinical features/CPT2 gene/Tandem mass spectrometry/Free carnitine/Case report引用本文复制引用
基金项目
上海市卫生健康委科研项目(202140346)
出版年
2024
NETL
NSTL
维普
万方数据