SUCLG1基因突变相关的新生儿致死性酸中毒1例并文献复习

SUCLG1 gene mutation related neonatal fatal acidosis:a case report and literature review

目的探讨SUCLG1基因突变所致新生儿脑肌病型线粒体DNA耗竭综合征9型(MDS)的临床特点,为其早期诊断提供依据。方法对广州市妇女儿童医疗中心新生儿科收治的1例新生儿脑肌病型MDS 9型患儿的临床表现、生化结果、辅助检查、尸体病理及基因报告进行回顾性分析,并以"线粒体DNA耗竭综合征""SUCLG1基因""甲基丙二酸尿症""甲基丙二酸""SUCLG1"等为关键词,分别对中国知网、万方、Pubmed、ClinVar自建库至2023年5月收录的文献进行检索,其中仅13篇文章报道20例新生儿期发病的SUCLG1基因突变导致的MDS,本文总结新生儿脑肌病型MDS 9型的临床特点。结果本例患儿为足月小样儿,女,生后0.5 h起病,主要表现为呼吸窘迫、难以纠正的代谢性酸中毒、高乳酸血症、低氧血症、尿甲基丙二酸和血氨轻度升高,予以禁食、呼吸循环支持、纠酸等治疗效果欠佳,生后5 d死亡。尸体病理见脑干蛛网膜下腔出血及血肿形成、动脉导管未闭、卵圆孔未闭、左肺动脉狭窄、右心室和左心室室壁增厚。外观及四肢未见畸形。血酰基肉碱提示C0含量极低,C3较正常高值升高3.7倍。尿液GC-MS见少量甲基丙二酸,全外显基因检测出SUCLG1基因c.901G>A(p.Gly301Arg)和c.315-316dup(p.Glu106GlyfsTer63)复合变异,确诊脑肌病型MDS 9型。共检索13篇文献20例新生儿期发病的脑肌病型MDS 9型患者,包括本例共21例,临床特征主要为新生儿期出现不明原因的肌张力减低、喂养困难,伴有甲基丙二酸轻度升高,95%有高乳酸血症,80%有呼吸窘迫,累及呼吸、循环系统者更易出现致死性乳酸酸中毒,全外显子基因测序示SUCLG1基因突变。治疗以支持为主,预后差,死亡率高。结论新生儿期不明原因的肌张力减低、喂养困难、乳酸酸中毒、甲基丙二酸轻度升高应警惕新生儿脑肌病型MDS 9型,累及呼吸、循环系统者更易出现新生儿致死性酸中毒,基因测序可帮助诊断。

Objective To investigate the clinical features of neonatal encephalomyopathic mitochondrial DNA depletion syndrome type 9(MDS)caused by SUCLG1 gene mutation,and to provide a basis for its early diagnosis.Methods The clinical data of a neonatal patient with encephalomyopathic MDS type 9,admitted to the Department of Neonatology at the Guangzhou Women and Children’s Medical Center,was analyzed retrospectively.This included an evaluation of the patient’s clinical manifestations,biochemical results,auxiliary examinations,autopsy pathology,and genetic reports.The key words of"mitochondrial DNA depletion syndrome""SUCLG1 gene""methylmalonic aciduria""methylmalonic acid""SUCLG1"were used.A literature search was performed in China National Knowledge Infrastructure(CNKI),Wanfang,Pubmed,and ClinVar from the establishment of the database to May 2023,Only 13 reports have documented 20 cases of neonatal-onset MDS resulting from SUCLG1 gene mutations.This article summarizes the clinical features of neonatal encephalomyopathic MDS type 9.Results The patient was a full-term small for gestational age girl.The main clinical manifestations were respiratory distress,metabolic acidosis,hyperlactacidemia,hypoxemia,urine methylmalonic acid and blood ammonia were slightly elevated.Fasting,respiratory and circulatory support and rectification of acid intoxication were not effective.Autopsy showed brain stem subarachnoid hemorrhage,hematoma formation,patent ductus arteriosus,patent foramen ovale,left pulmonary artery stenosis,right ventricular and left ventricular wall thickening.There were no deformities in appearance or limbs.Acylcarnitines in blood showed that C0 was extremely low and C3 was 3.7 times higher than the normal high value.Urine GC-MS showed A small dose of methylmalonic acid,and the whole exon gene detection of SUCLG1 gene c.901G>A(p.Gly301Arg)and c.315-316dup(p.Glu106GlyfsTer63)compound mutations.Encephalomyopathic mitochondrial DNA depletion syndrome 9 was diagnosed.A total of 21 cases(including this case)of neonatal-onset encephalomyopathic MDS type 9 were retrieved from 13 articles.The main clinical features were unexplained hypotonia and feeding difficulties accompanied by mild elevation of methylmalonic acid,95%hyperlacticemia,and 80%respiratory distress.Patients with respiratory and circulatory system involvement are more likely to develop fatal lactic acidosis.Whole exome sequencing showed SUCLG1 gene mutation.Treatment is mainly supportive,with poor prognosis and high mortality.Conclusions Unexplained hypotonia,feeding difficulties,lactic acidosis and mild elevation of methylmalonic acid in the neonatal period should be considered for neonatal encephalomyopathy mitochondrial DNA depletion syndrome 9.Patients with respiratory and circulatory involvement are more likely to have neonatal fatal acidosis.Gene sequencing can help with the diagnosis.