Clinical and genetic characteristics of 3 cases of holocarboxylase synthetase deficiency and literature review
10.11855/j.issn.0577-7402.1619.2025.0523
- VernacularTitle: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
- Author:
Li-Ming ZHANG
1
;
Wei YANG
;
Ying-Xian ZHANG
;
Hai-Hua YANG
;
Xiao-Lei LI
;
Qian-Ying LI
;
Jian-Wei YANG
;
Jun-Mei YANG
;
Yong-Xing CHEN
Author Information
1. 郑州大学附属儿童医院/河南省儿童医院郑州儿童医院检验科/郑州市儿童感染与免疫重点实验室,河南郑州 450018
- Keywords:
holocarboxylase synthetase deficiency;
HLCS gene;
whole-exome sequencing
- From:
Medical Journal of Chinese People's Liberation Army
2025;50(8):984-990
- CountryChina
- Language:Chinese
-
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.
