Clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency:an analysis of six cases
10.7499/j.issn.1008-8830.2404026
- VernacularTitle:3-甲基巴豆酰辅酶A羧化酶缺乏症6例患儿的临床特征及遗传学分析
- Author:
Li-Ming ZHANG
1
;
Sheng-Nan WU
;
Ya-Nan GUO
;
Jian-Wei YANG
;
Hong-Qi SUN
;
Jun-Mei YANG
;
Yong-Xing CHEN
Author Information
1. 郑州大学附属儿童医院检验科/郑州市儿童感染与免疫重点实验室,河南郑州 450018
- Keywords:
3-Methylcrotonoyl-coenzyme A carboxylase deficiency;
3-Hydroxyisovalerylcarnitine;
3-Hydroxyisovalerate;
3-Methylcrotonyl-glycine;
MCCC1 gene;
MCCC2 gene;
Child
- From:
Chinese Journal of Contemporary Pediatrics
2024;26(8):845-851
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency(MCCD).Methods A retrospective analysis was conducted on the clinical manifestations and genetic testing results of six children with MCCD who attended Children's Hospital Affiliated to Zhengzhou University from January 2018 to October 2023.Results Among the six children with MCCD,there were 4 boys and 2 girls,with a mean age of 7 days at the time of attending the hospital and 45 days at the time of confirmed diagnosis.Of all children,one had abnormal urine odor and five had no clinical symptoms.All six children had increases in blood 3-hydroxyisovaleryl carnitine and urinary 3-hydroxyisovaleric acid and 3-methylcrotonoylglycine,and five of them had a reduction in free carnitine.A total of six mutations were identified in the MCCC1 gene,i.e.,c.1630del(p.R544Dfs*2),c.269A>G(p.D90G),c.1609T>A(p.F537I),c.639+2T>A,c.761+1G>T,and c.1331G>A(p.R444H),and three mutations were identified in the MCCC2 gene,i.e.,c.838G>T(p.D280Y),c.592C>T(p.Q198*,366),and c.1342G>A(p.G448A).Among these mutations,c.269A>G(p.D90G)and c.1609T>A(p.F537I)had not been previously reported in the literature.There was one case of maternal MCCD,and the child carried a heterozygous mutation from her mother.Five children with a reduction in free carnitine were given supplementation of L-carnitine,and free carnitine was restored to the normal level at the last follow-up visit.Conclusions This study identifies two new mutations,c.269A>G(p.D90G)and c.1609T>A(p.F537I),thereby expanding the mutation spectrum of the MCCC1 gene.A combination of blood amino acid and acylcarnitine profiles,urine organic acid analysis,and genetic testing can facilitate early diagnosis and treatment of MCCD,and provide essential data for genetic counseling.
