一例转钴胺素Ⅱ缺乏症患儿的临床及遗传学分析

Clinical and genetic analysis of a child with transcobalaminⅡdeficiency

目的探讨1例表现为全血细胞减少、生长发育落后、肺部感染患儿可能的遗传学病因及其临床诊治。方法采集患儿及其正常表型双亲的外周血样,提取基因组DNA,应用高通量测序的方法对患儿行血液系统相关疾病基因检测。结果患儿TCN2基因存在3个变异,分别是第5外显子上游c.581-8A>T,该变异患儿父母均携带;第6外显子c.924_927del,该变异来源于母亲;第7外显子c.973C>T,该变异为新发变异。经基因变异致病性分析结合患儿临床表现、三系减少、血甲基丙二酸及同型半胱氨酸增高,确诊其为转钴胺素Ⅱ缺乏症。该患儿出现呼吸道感染表现,经肺部影像学检查及肺泡灌洗液病原学高通量测序证实为耶氏肺孢子虫病,在给予肌注维生素B12治疗过程中患儿出现急性呼吸窘迫综合征,经复方磺胺甲恶唑抗感染及对症支持治疗后好转。结论我们报道了1例转钴胺素Ⅱ缺乏症患儿,发现了该基因的新变异,分析了该基因3个变异的致病性。钴胺素治疗该病应个体化。

Objective To investigate the genetic etiology,clinical diagnosis and treatment of a child with pancytopenia,failure to thrive and pulmonary infection.Methods Peripheral blood samples of the child and her parents were collected.Genomic DNA was extracted.Genetic variants associated with hematological diseases were detected by high-throughput sequencing.Results Three variants ofTCN2 gene were found,one of which located in exon 5 upstream(c.581-8A>T),the parents has carried this variant;one in exon 6(c.924_927del),the variant was originated from the mother;one in exon 7(c.973C>T),the variant has ocurred de novo.The variants pathogenic analysis combined with clinical manifestation,pancytopenia,the increase in methylmalonic acid level and increased homocysteine,the child was diagnosed with transcobalaminⅡdeficiency.The patient presented with respiratory infection,which was confirmed to be pneumocystosis by lung radioscopy and pathogenic high throughput sequencing of broncho-alveolar lavage fluid.The patient presented with acute respiratory distress syndrome during the treatment with intramuscular injection of vitamin B12,and improved after anti-infection with compound sulfamethoxazole and symptomatic support treatment.Conclusion We reported a case of Chinese child with TCNⅡdeficiency due to novel gene variant,and analyzed the pathogenicity of the three variants.The treatment of TCNⅡdeficiency with cobalamin should be individualized.