目的 探讨cblC型甲基丙二酸血症患儿的临床特点、实验室检查及基因型的关系,为早期诊断提供思路与方法。方法 收集2015-2020年河北医科大学第二医院小儿内分泌与生长发育科诊治的甲基丙二酸血症患儿19例,对其临床表现、基因结果、串联质谱分析及影像学检查等资料进行回顾性分析。结果 19例中男性10例,女性9例,8例通过新生儿筛查确诊。基因检测共发现13种变异,其中以c.609G>A突变最多,其次为c.80A>G、c.656_ c.658delAGA。11例非新生儿筛查确诊的患儿均以神经系统症状为首发表现,包括喂养困难、发育落后、反应差、视力障碍、抽搐等。串联质谱分析中C3/C0、C3/C2、尿甲基丙二酸和同型半胱氨酸明显增高。实验室检测有多脏器损伤,累及血液、神经及消化等系统。结论 cblC型甲基丙二酸血症患儿临床表现和实验室检查表现多样且缺乏特异性,基因型为终止或移码突变者多呈早发型且症状较重,可表现为脑积水等严重神经系统并发症;晚发型症状较轻且早期治疗后预后良好。由于患儿发病较晚常常容易忽略,导致病情延误,因此cblC型甲基丙二酸血症的早期诊断十分重要,可极大地改善病情及预后。新生儿串联质谱筛查有助于此病的早期诊断,基因型检测有助于明确类型并进行针对性治疗,降低致残率及病死率。

Objective To provide thinking and measures for early diagnosis by exploring the relations between clinical characteristics, laboratory examination and genotypes of cblC type methylmalonic acidemia.Methods The data of clinical manifestation, gene results, tandem mass spectrometry, imageological examination of 19 children with methylmalonic acidemia admitted to the Department of Pediatric Endocrinology and Growth Development, the Second Hospital of Hebei Medical University from 2016 to 2020 were retrospectively analyzed. Results There were 10 male and 9 female patients in out of 19 cases, of which 8 cases were confirmed by neonatal screening. A total of 13 mutations were found by genetic testing, the most common mutations satisfied c.609G>A, followed by the mutations satisfying c.80A>G and c.656_ c.658delAGA. Initial neurological symptoms of 11 cases who were not confirmed by neonatal screening were feeding difficulties, developmental delay, poor response, visual impairment, convulsions, etc. C3 /C0, C3 /C2, urinary methylmalonic acid and homocysteine were significantly elevated in tandem mass spectrometry. Laboratory testing data showed that multiple organs were damaged involving the blood system, nervous and digestive systems, etc. Conclusion The clinical manifestations and laboratory examination of children with cblC type methylmalonic acidemia demonstrate diversely with poor specificity. The genotypes showing the termination or frame-shift mutation normally develop early and have relatively severe symptoms may be show severe neurological complications including the hydrocephalus. The late-onset conditions are mild and have better prognosis by early treatment. late-onset disease of children is easily ignored normally, causing delayed diagnosis on pathogenetic condition. It is necessary to take early diagnosis on cblC type methylmalonic acidemia Attributing to great improvements of the condition and prognosis. Neonatal tandem mass spectrometry screening makes for the early diagnosis, and genotype detection contribute to specific disease classification and targeted treatment, thereby reducing the disability rate and mortality of the disease.