Objectives: 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.
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。.
Keywords: CPT2 gene; Carnitine palmitoyltransferase 2 deficiency; Case report; Clinical features; Free carnitine; Tandem mass spectrometry.