Clinical features and genetic analysis of three children with β -ketothiolase deficiency
10.3760/cma.j.cn511374-20221109-00775
- VernacularTitle:β-酮硫解酶缺乏症3例患儿的临床及遗传学分析
- Author:
Xue WU
1
;
Yuan LI
;
Qiong CHEN
;
Shengnan WU
;
Chang SU
;
Dongxiao LI
;
Yongxing CHEN
;
Haiyan WEI
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:
Acetyl-CoA C-Acyltransferase;
β-ketothiolase deficiency;
Hypoglycemia;
Ketoacidosis;
2-methyl-3-hydroxybutyrate;
ACAT1 gene
- From:
Chinese Journal of Medical Genetics
2024;41(3):289-293
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD).Methods:Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children′s Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed.Results:The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c. 1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c. 121-3C>G and c. 826+ 5_826+ 9delGTGTT in child 2, and c. 928G>C and c. 1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c. 1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+ PP3+ PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. Conclusion:The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.
