解放军医学杂志2025，Vol.50Issue(8)：984-990,7.DOI:10.11855/j.issn.0577-7402.1619.2025.0523
全羧化酶合成酶缺乏症3例临床及遗传学特征分析并文献复习
Clinical and genetic characteristics of 3 cases of holocarboxylase synthetase deficiency and literature review
摘要
Abstract
Objective To explore the clinical and genetic characteristics of children with holocarboxylase synthetase(HLCS)deficiency.Methods A retrospective analysis was conducted on the clinical data of 3 children with HLCS deficiency who were admitted to Children's Hospital Affiliated to Zhengzhou University from December 2014 to January 2024.Relevant literature indexed in CNKI,Wanfang Data,PubMed and other databases was reviewed to summarize the clinical characteristics and HLCS gene mutations of children with HLCS deficiency.Results All 3 children were male,with onset age of 4-6 months.The main clinical manifestations included shortness of breath,vomiting,diarrhea,and poor mental state,and partial cases were complicated by growth retardation and neurological symptoms.Laboratory tests showed metabolic acidosis in all cases,blood amino acid and acylcarnitine profiles as well as urinary organic acid analysis suggested multiple carboxylase deficiency.Genetic testing revealed compound heterozygous mutation in the HLCS gene of all 3 children,among which the c.1892delT(p.L631X)mutation was previously unreported.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the c.1892delT(p.L631X)mutation was rated as pathogenic mutation(PVS1+PM2_supporting+PM3).Biotin supplementation was effective in all cases.Literature review included 27 English literatures and 29 Chinese literatures,reporting a total of 133 children with HLCS deficiency caused by HLCS gene mutation.Common clinical manifestations included metabolic acidosis,skin lesions,vomiting,feeding difficulties,dyspnea,diarrhea,and neurological symptoms,etc.Conclusions Blood amino acid and acylcarnitine profiles,urine organic acid analysis,and gene testing are helpful for the diagnosis of HLCS deficiency.Timely biotin supplementation leads to a good prognosis.The mutation of HLCS gene is considered as the genetic etiology of HLCS deficiency in 3 children,among which the c.1892delT(p.L631X)mutation is a newly discovered mutation.关键词
全羧化酶合成酶缺乏症/HLCS基因/全外显子组测序Key words
holocarboxylase synthetase deficiency/HLCS gene/whole-exome sequencing分类
医药卫生引用本文复制引用
张利明,杨威,张英娴,杨海花,李小磊,李倩影,杨建伟,杨俊梅,陈永兴..全羧化酶合成酶缺乏症3例临床及遗传学特征分析并文献复习[J].解放军医学杂志,2025,50(8):984-990,7.基金项目
河南省重点研发专项(251111311300) （251111311300）
河南省科技发展计划(232102311109) （232102311109）
河南省医学科技攻关计划联合共建项目(LHGJ20240560) （LHGJ20240560）
河南省儿童遗传代谢性疾病重点实验室开放课题(SS202205) This work was supported by the Henan Provincial Key Research and Development Special Project(251111311300),the Henan Provincial Science and Technology Development Program(232102311109),the Medical Science and Technology Development Program of Henan Province(LHGJ20240560),and the Henan Provincial Key Laboratory of Children's Inherited Metabolic Diseases Open Subject(SS202205) （SS202205）
