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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.
ABSTRACT
Objective To analyze the clinical characteristics and gene mutations of 56 patients with congenital hyperinsulinism(CHI)and to provide a theoretical basis for clinical diagnosis and treatment of CHI.Methods Fifty-six children who were diagnosed as CHI between February 2002 and January 2016 in Beijing Children's Hospital Affiliated to Capital Medical University were selected as research subjects.A retrospective study was done about the clinical data and the treatment procedures of the 56 patients,such as perinatal conditions,clinical manifestations,laboratory data,treatments,prognosis and so on.Polymerase chain reaction(PCR)-DNA technology or next-generation sequencing technology was used to analyze the CHI relevant genes of the 56 patients.Results Thirty of the 56 patients carried CHI gene mutation.(1)Twenty-three of 56 patients(41.0％)carried ABCC8/KCNJ11 gene mutations:4 of 23 patients carried complex heterozygous mutation,1 of 23 patients carried both ABCC8 and KCNJ11 gene mutation,1 of 23 patients carried maternally inherited ABCC8 gene mutation,12 of 23 patients carried paternally inherited ABCC8 gene mutation,1 of 23 patients carried paternally inherited KCNJ11 gene mutation,3 of 23 patients carried de novo ABCC8 gene mutation,1 of 23 patients had unknown genetic way,19 of 23 patients were treated with Diazoxide,2 of 19 patients were responsive to Diazoxide,7 of 19 patients were unresponsive to Diazoxide and 10 of 19 patients were uncertain to Diazoxide.(2)Five of 56 patients(8.9％)carried GLUD1 gene mutation,4 of 5 patients were treated with Diazoxide and they were all responsive to Diazoxide.(3)One of 56 patients(1.7％)carried de novo GCK gene mutation,responsive to Diazoxide treatment.(4)One of 56 patients(1.7％)carried maternally inherited SLC16A1 gene mutation,responsive to Diazo-xide treatment.Conclusions The ABCC8 gene and GLUD1 gene mutation are the main causative genes of CHI.The GCK gene and SLC16A1 gene mutation are in the minority.Most ABCC8 gene and KCNJ11 gene mutation are unresponsive to Diazoxide treatment.