摘要
目的探讨1例全羧化酶合成酶缺乏症(HCSD)患儿的临床和遗传学特点。方法回顾性分析2014年8月在山东大学齐鲁儿童医院儿科确诊为HCSD的1例患儿的临床资料。该患儿家属签署知情同意书,符合医学伦理学规定。患儿女,1岁6个月,因"呕吐伴腹泻3 d,发热2 d"入院。患儿反应差,出现代谢性酸中毒且纠酸治疗效果差,尿有机酸检测结果示3–羟基异戊酸、3–羟基丙酸、3–甲基巴豆酰甘氨酸、乳酸、丙酮酸水平均高于正常水平。采用二代测序技术对全羧化酶合成酶(HLCS)基因进行突变检测,再应用Sanger测序技术对上述检测到的突变进行验证。结果二代测序技术和Sanger测序验证表明,该患儿的HLCS基因外显子有两处杂合突变点:c.1080A>C和c.782delG。其中,c.1080A>C导致氨基酸改变即p.R360S;c.782delG导致氨基酸移码突变。患者的基因突变由父母遗传而来,c.1080A>C来源于父亲,c.782delG来源于母亲。给患儿进行针对性治疗后,患儿症状消失。结论 HCSD的临床表现缺乏特异性,二代和Sanger测序技术可以发现患儿HLCS基因存在的致病突变,从而在基因水平上确诊HCSD。
Objective To investigate the clinical and genetic characteristics of holocarboxylasesynthetase deficiency(HCSD)in a case.Methods Clinical data of a child diagnosed with HCSD in Qilu Children'sHospital of Shandong University in August2014was retrospectively studied.The informed consent of the patient’sparents was obtained and the local ethical committee approval had been received.The child patient was female,1yearand6months old.She was admitted to hospital because of vomiting along with diarrhea for3days and fever for2days.Her mental reaction was poor,and she had metabolic acidosis,but the treatment effect of correcting acidosis was poor.Urine organic acid test showed that the levels of3-hydroxy isovaleric acid,3-hydroxypropionic acid,3-methyl crotonicacyl glycine,lactic acid and pyruvate in this child were higher than those in normal child.Mutations in holocarboxylasesynthetase(HLCS)gene were detected using the second generation sequencing technology and then verified by Sanger.Results The second generation sequencing and Sanger verification showed that two heterozygous mutations,c.1080A>C and c.782delG,were found in exons of the HLCS gene in this child.c.1080A>C leads toamino acid change,that is p.R360S;and c.782delG leads to amino acid frameshift.The child patient's geneticmutations were inherited from her parents,c.1080A>C from her father and c.782delG from her mother.Theclinical symptoms disappeared after targeted treatments.Conclusions HCSD lacks of specificity in clinicalmanifestations.The second generation and Sanger sequencing techniques can reveal HLCS gene mutations in child patient and then confirmed HCSD at the gene level.
作者
张豪正
王广新
Zhang Haozheng;Wang Guangxin(Medical Institute of Paediatrics,Qilu Children’s Hospital of Shandong University,Jinan 250022,China)
出处
《中华肥胖与代谢病电子杂志》
2017年第2期82-85,共4页
Chinese Journal Of Obesity and Metabolic Diseases：Electronic Edition
基金
山东省医药卫生科技发展计划项目(2013WS0003)
济南市科学技术发展计划项目(201602195)
作者简介
通讯作者：王广新，Email:wanggxemail@163.com
