Clinical and genetic characteristics analysis of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinemia
10.3760/cma.j.issn.1674-1935.2020.01.009
- VernacularTitle: 中国儿童谷氨酸脱氢酶型先天性高胰岛素血症临床及遗传学特征分析
- Author:
Ge LYU
1
;
Zidi XU
2
;
Peipei HUI
2
;
Qiao ZENG
2
;
Min LIU
2
;
Jie YAN
2
;
Yuyun WU
2
;
Yanmei SANG
2
Author Information
1. Department of Laboratory Center, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
2. Department of Endocrinology, Genetic and Metabolism Center, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China
- Publication Type:Journal Article
- Keywords:
Congenital;
Hyperinsulinism;
Glutamate dehydrogenase;
Mutation;
GLUD1 gene
- From:
Chinese Journal of Pancreatology
2020;20(1):47-51
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features and genetic characteristics of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinism (GDH-HI).
Methods:Pedigrees with 10 GDH-HI children admitted to Beijing Children′s Hospital from February 2008 to December 2018 were selected as subjects. Clinical features, the detection of pathogenic genes and follow-up data were retrospectively analyzed. Polymerase chain reaction DNA (PCR-DNA) direct sequencing method and second generation sequencing technique were used to analyze the GLUD1 genetic sequences of 10 GDH-HI children and their relatives.
Results:Of the 10 GDH-HI children, 9 had normal birth weight and 1 was a giant. Nine patients were accompanied by asymptomatic hyperammonemia, and one had normal blood ammonia. 9 had ever been treated with diazoxide, which was all effective. All 10 children carried GLUD1 gene mutations, 5 patients carried c. 965C>T (p.R322H) GLUD1 gene mutation, and the remaining 5 cases carried c. 1388A>T (p.N463I), c. 1495C>A(p.G499C), c. 1493C>T(p. S498L), c. 1519G>A(p.H507Y) and c. 1388A>G(p.N463S), respectively. 9 cases (90%) had de novo mutations, and 1 case had paternal autosomal dominant inheritance. 8 children were followed up in long term. One child had spontaneous remission in 8 years after being diagnosed, and seven patients required long-term oral diazoxide to maintain normal blood glucose levels, two of whom had epilepsy.
Conclusions:The birth weight of children with GDH-HI in China was usually normal. A small number of GDH-HI children had normal serum ammonia levels. Most of the GLUD1 gene mutations in GDH-HI children in China were de novo mutations, among which the GDH p. R322H mutation was a hot spot mutation in Chinese children with GDH-HI. Most of GDH-HI children were diazoxide-responsive. As the disease progresses, some children may have epilepsy, and a few children have a tendency to relieve by themselves.
