Abstract: The clinical and molecular hereditary of a child died of HLCS deficiency in May， 2020 in the Fourth Hospital of Baotou were retrospectively reviewed. The child，a 2-month-and-29cl old boy，was admitted to hospital due to sputum in the throat for 5 days，convulsions for 1 day and coma for 12 hours. He was poorly responsive and his metabolic acidosis was intractable. Two days later，the patient asked for discharged and died on the day of his returning home. Blood tandem mass spectrometry showed a significant increase in 3-hydroxyisovaleryl carnitine and propionyl carnitine. Urine gas chromatography mass spectrometry showed a significant increase in 3-hydroxypropionic acid，propionylglycine，methylcrotonylglycine and methylcitricacid. Whole exome sequencing showed there was a compound heterozygous mutation of the c.1522C>T （p.R508W）/c.782delG （p.G260V） in the HLCS. The Sanger family verified that the mutations were derived from their parents. The clinical presentations of HLCS deficiency are atypical. In children with severe pneumonia combined with epilepsy and intractable metabolic acidosis，HLCS deficiency should be considered and the diagnosis should be confirmed early by timely MS/MS，GC/MS screening and genetic analysis.

Key words: holocarboxylase synthetase deficiency, HLCS gene, clinical feature, child

摘要： 回顾性分析2020年5月包头市第四医院收治的1例确诊为全羧化酶合成酶缺乏症的死亡婴儿的临床和分子遗传学资料。患儿男，2月龄29 d，因“喉中痰鸣5 d，抽搐1 d，昏迷半天”入院。反应差，代谢性酸中毒难以纠正，经积极治疗2 d后病情仍进一步加重，自动出院，返家当日死亡。血氨基酸及及酰基肉碱分析示3-羟基异戊酰肉碱及丙酰肉碱增高。尿液有机酸分析示3-羟基丙酸、丙酰甘氨酸、甲基巴豆酰甘氨酸、甲基枸橼酸升高。采用全外显子组测序示HLCS存在c.1522C>T（p.R508W）/c.782delG（p.G260V）复合杂合突变，经Sanger家系验证突变来源于父母。HLCS缺乏症临床表现不典型，对于重症肺炎合并癫痫及难以纠正的代谢性酸中毒患儿，应考虑HLCS缺乏症可能，及时行代谢筛查及基因分析确诊。

关键词: 全羧化酶合成酶缺乏症, HLCS基因, 临床特点, 儿童