线粒体DNA耗竭综合征患儿1例的临床特征及SUCLG1基因变异分析  

The analysis on clinical characteristics and SUCLG1 gene variation for a patient with mitochondrial DNA depletion syndrome

作　　者：纪可佳 张改秀[2] 范馨 朱彤 赵润涵 JI Kejia;ZHANG Gaixiu;FAN Xin;ZHU Tong;ZHAO Runhan(Pediatrics and Education and Research Office of Shanxi Medical University,Taiyuan,Shaanxi 030001,China;Endocrine and Genetic Metabolism Section,Children’s Hospital of Shanxi,Taiyuan,Shaanxi 030001,China)

机构地区：[1]山西医科大学儿科教研室,山西太原030001 [2]山西省儿童医院内分泌与遗传代谢科,山西太原030001

出　　处：《中国优生与遗传杂志》2023年第11期2298-2302,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的 探讨1例线粒体DNA耗竭综合征9型(MTDPS9)患儿的临床表现及遗传学特征。方法 回顾分析1例SUCLG1基因相关MTDPS9患儿的临床资料,对其进行全外显子组测序,用Sanger测序对候选变异进行验证。结果 患儿,女,生后4个月以多汗就诊,抬头不能,生长发育迟缓,肌张力低下,中度智力缺陷,伴听力严重受损。肝功能异常,血清乳酸、丙酮酸升高,丙酰肉碱、丁二酰肉碱升高,C3/C2正常;尿液甲基丙二酸及其代谢产物浓度轻度升高,提示甲基丙二酸尿症。头颅MRI显示双侧脑室体后部旁白质T2W1信号略偏高,双侧额部脑外间隙及前纵裂池稍宽。基因测序示SUCLG1基因存在c.550G>A(p.G184S)与c.721_c.722delGA(p.E241Nfs16)复合杂合变异,确诊该患儿为线粒体DNA耗竭综合征9型,其中,c.721_c.722delGA既往未见报道。结论 c.721_c.722delGA的检出扩展了SUCLG1基因的变异谱,为患儿的临床诊断和遗传咨询提供了依据。当患儿出现不明原因的生长发育落后、智力缺陷、肌张力低下、听力障碍伴高乳酸血症、轻度甲基丙二酸尿症时,应高度警惕本病,基因分析有助于明确诊断。Objective To explore the clinical characteristics and genetic basis on a child with mitochondrial DNA depletion syndrome type 9(MTDPS9).Methods The clinical data of a child with SUCLG1 gene-associated MTDPS9 were retrospectively analyzed.The whole exome sequencing was performed on the child,and the candidate variant was verified by Sanger sequencing.Results The proband,a female,presented with hyperhidrosis at the 4th month after birth,inability to raise her head,growth retardation,muscular hypotonia,moderate intellectual deficiency,and severe hearing impairment.Laboratory tests showed liver damage,blood lactic acid and pyruvate increased,propionylcarnitine and succinylcarnitine increased,and normal C3/C2.Urinary organic acid analysis showed mildly elevated concentrations of methylmalonic acid and its metabolites,indicating methyl malonic aciduria.Cranial MRI showed a slightly elevated voiding-mass T2W1 signal in the posterior parietal white matter of the posterior ventricular body bilaterally,with a slightly wider frontal-extracerebral space and anterior longitudinal fissure cisterns.Genetic sequencing showed two heterozygous mutations in SUCLG1 gene of c.550G>A(p.G184S)and c.721_c.722delGA(p.E241Nfs16),confirming the diagnosis of mitochondrial DNA depletion syndrome type 9.The c.721_c.722delGA had not been previously reported as a new mutation.Conclusion The detection of c.721_c.722delGA extended the spectrum of SUCLG1 gene variants and provided a basis for the clinical diagnosis and genetic counseling of affected children.When a child presents with unexplained growth retardation,intellectual deficiency,muscular hypotonia,hearing impairment together with increased blood pyruvic acid and lactic acid,and mild methylmalonic acidemia,mitochondrial DNA depletion syndrome should be considered.And genetic analysis can help to clarify the diagnosis.

关 键 词：线粒体DNA耗竭综合征 SUCLG1基因 甲基丙二酸尿症 发育迟缓 多汗 

分 类 号：R725.9[医药卫生—儿科]