探讨谷胱甘肽合成酶缺乏症(GSSD)患儿的临床特征及谷胱甘肽合酶(GSS)基因突变特点。

选择2017年9月，于中山大学附属第六医院确诊的1例GSSD患儿为研究对象。回顾性分析其临床表现、实验室检查及基因检测结果等临床病例资料。以"谷胱甘肽合成酶缺乏症""焦谷氨酸尿症""glutathione synthase deficiency""GSSD"为关键词，对万方数据知识服务平台及PubMed数据库，自2010年1月至2020年5月收录的关于GSSD患儿诊治研究相关文献进行检索，并总结GSSD患儿的临床表现和基因突变特点。本研究经中山大学附属第六医院伦理委员会批准(审批文号：2017ZSLYEC-105)，患儿监护人签署知情同意书。

①临床特点及转归：本例患儿为女性，4 d龄，因"生后进行性呼吸困难4 d"入院。患儿临床表现为中度贫血、重度代谢性酸中毒、焦谷氨酸尿症及中枢神经系统影像学改变，并有类似GSSD临床表现的家族史(其同胞姐姐4 d龄时发病，放弃治疗后50⁺ d龄时死亡)。经治疗后，本例患儿呼吸困难缓解，但仍然存在代谢性酸中毒。经基因检测确诊为GSSD(重型)后，监护人放弃治疗，患儿于2个月龄时死亡。②基因检测结果：本例患儿为GSS基因c.491G>A和c.800G>A复合杂合突变，分别遗传自母亲和父亲。③文献复习结果：检索到10篇关于GSSD患儿诊治研究相关文献，共计纳入15例GSSD患儿，包括轻、中、重型GSSD各为2、2、11例。轻、中型患儿(共4例)经早期诊断、积极干预达临床治愈；重型患儿(11例)中，3例生后5个月内死亡，8例存活儿均遗留神经系统后遗症。12例患儿接受基因检测的结果显示，共检出11种GSS基因突变，其中6例检出GSS基因c.491G>A突变患儿的临床表型均为中或重型。

GSSD临床表现具有特异性，可有家族遗传性。该病由GSS基因突变所致，其基因突变类型与临床表型的关系，尚需进一步研究。早期诊断及治疗，可提高该病患者生存率、改善长期预后。

To investigate clinical features and characteristics of glutathione synthase (GSS) gene mutation in children with glutathione synthase deficiency (GSSD).

A case of GSSD child who was diagnosed in the Sixth Affiliated Hospital of Sun Yat-sen University in September 2017 was selected as research subject. Her clinical data including clinical manifestations, laboratory examinations and genetic test results were analyzed retrospectively. Literature of studying on diagnosis and treatment of children with GSSD were retrieved with key words of " glutathione synthase deficiency" " pyroglutamic aciduria" in Chinese and " glutathione synthase deficiency" " GSSD" in English, based on Wanfang Data Knowledge Service Platform and PubMed database from January 2010 to May 2020, and to summarize clinical manifestations and gene mutation characteristics of them. This study was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (approval No. 2017ZSLEC-105), and guardians of this child signed the informed consent.

① Clinical features and outcomes: a 4-day-old girl who was hospitalized with clinical symptom of " progressive dyspnea 4 d after birth" . She presented with moderate anemia, severe metabolic acidosis, pyroglutamic aciduria and central nervous system imaging abnormal, also with family history of similar clinical manifestations (her sibling elder sister had similar symptom at 4 d old and died at 50⁺ d old after being give up treatment). Her dyspnea was relieved after treatment, but metabolic acidosis remained intractable. After being diagnosed as GSSD (severe type) by genetic testing, her guardians gave up treatment, and she died at 2 months old. ② Genetic test results: she had two heterozygous mutations in GSS gene inherited from her mother and father which were c. 491G>A and c. 800G>A. ③ Literature review results: a total of 10 pieces of literature studying on diagnosis and treatment of children with GSSD were retrieved, and 15 children were included, including 2 mild, 2 moderate and 11 severe GSSD, respectively. Mild and moderate GSSD children (4 cases) could be cured by early diagnosis and active medical intervention. Among 11 cases of severe GSSD children, 3 died within 5 months after birth and 8 survival children had neurological sequelae. There were 11 types of GSS gene mutations in 12 children who got genetic testing, 6 of them with c. 491G>A mutation in GSS gene and their clinical phenotypes were moderate or severe.

GSSD might runs in families, whose clinical manifestations are specific. GSSD is caused by GSS gene variation, the relationship between types of mutation in GSS gene and clinical phenotypes remains to be further studied. Early diagnosis and treatment can improve survival rate and long-term prognosis of GSSD patient.