Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
10.3760/cma.j.cn511374-20221010-00677
- VernacularTitle:3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症2例患儿的临床及遗传学分析
- Author:
Xue WU
1
;
Dongxia FU
;
Huizhen WANG
;
Shengnan WU
;
Dongxiao LI
;
Yongxing CHEN
Author Information
1. 郑州大学附属儿童医院、河南省儿童医院、郑州儿童医院内分泌遗传代谢科，郑州 450053
- Keywords:
3-hydroxy-3-Methylglutaryl-CoA lyase deficiency;
Hypoglycemia;
Metabolic acidosis;
HMGCL gene
- From:
Chinese Journal of Medical Genetics
2024;41(2):199-204
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).Methods:Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively.Results:Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of the HMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of the HMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4). Conclusion:Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.
