Analysis of clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia that is spontaneously relieved.

OBJECTIVE: This study aimed to analyze the clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia (CHI) that is spontaneously relieved. METHODS: The patient group comprised 200 children with CHI that were treated at the Beijing Children's Hospital from January 2006 to December 2018. The patients were divided into two groups according to their prognosis: the spontaneous remission group (n = 92) and the nonspontaneous remission group (n = 108). The clinical characteristics, pathogenic genes, diagnosis and treatment process, and follow-up data of both groups were analyzed retrospectively. RESULTS: Of the 200 children with CHI, 92 achieved spontaneous remission. The age of spontaneous remission was between one month and nine years, and 47 of the children were relieved before the age of one year. The median age of onset was 85 days (range: 1-2825 days) in the spontaneous remission group and 2 days (range: 1-210 days) in the nonspontaneous remission group (P < 0.05). The mean birth weight was 3.44 ± 0.76 kg for the spontaneous remission group and 3.95 ± 0.75 kg for the nonspontaneous remission group (P < 0.05). Of the 92 children in the spontaneous remission group, 65 were treated with diazoxide with effective rate of 81.5% (53/65). In 12 cases in which diazoxide treatment failed, octreotide was used with an effective rate of 83.3% (10/12). Of the 108 children in the nonspontaneous remission group, 88 were treated with diazoxide with an effective rate of 43.2 % (38/88), and 29 children were treated with octreotide with an effective rate of 48.28% (14/29). Of the 30 children in the spontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 10 children (10/30, 33.3%) carried mutations. Of the 48 children in the nonspontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 37 children (37/48, 77.1%) were found to carry mutations. All of the differences in the indices mentioned above were statistically significant. CONCLUSIONS: The rate of spontaneous remission of CHI was significantly higher in children with late age of CHI onset, light birth weight, effective diazoxide treatment, and no common pathogenic gene mutations. Spontaneous remission was also possible for a small number of children that carried mutations in the ABCC and KCNJ11 genes and in whom diazoxide treatment failed.

Analysis on the pathogenic genes of 60 Chinese children with congenital hyperinsulinemia.

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children's Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, 8 patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. Conclusions: ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children's families has an important guiding significance for treatment planning and prognosis assessment.