Analysis of clinical features and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency
10.3760/cma.j.cn511374-20230611-00355
- VernacularTitle:迟发型多种酰基辅酶A脱氢酶缺乏症3例患儿的临床及遗传学分析
- Author:
Mengqin WANG
1
;
Xi WANG
;
Ang MA
;
Yu GU
;
Xiaotong ZHAO
;
Yaodong ZHANG
;
Dongxiao LI
;
Yongxing CHEN
;
Haiyan WEI
Author Information
1. 郑州大学附属儿童医院 河南省遗传代谢性疾病重点实验室 河南省儿童神经发育工程研究中心，郑州 450018
- Keywords:
Genetic disease;
Late-onset multiple acyl-CoA dehydrogenase deficiency;
ETFDH gene;
Blood tandem mass spectrum;
Urine gas chromatography-mass spectro
- From:
Chinese Journal of Medical Genetics
2024;41(7):790-796
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.
