Original Article

Clinical Management and Gene Mutation Analysis of Children with Congenital Hyperinsulinism in South China

10.4274/jcrpe.galenos.2019.2019.0046

  • Xu A
  • Jing Cheng
  • Huiying Sheng
  • Zhe Wen
  • Yunting Lin
  • Zhihong Zhou
  • Chunhua Zeng
  • Yongxian Shao
  • Cuiling Li
  • Li Liu
  • Xiuzhen Li

Received Date: 05.04.2019 Accepted Date: 10.06.2019 J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 31208162

Objective:

To explore the clinical presentation and molecular genetics characteristics of a group of CHI patients in southern China and explore the appropriate therapeutic approaches.

Methods:

We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was carried out for KCNJ11 and ABCC8 genes. The GLUD1 gene was sequenced in patients with hyperammonaemia. GCK gene sequencing was performed in those patients with no mutation identified in the ABCC8, KCNJ11 or GLUD1 genes.

Results:

ABCC8 mutations were identified in 16 children (25% of the cohort), GLUD1 mutations were identified in 5 children, and no KCNJ11 or GCK genetic mutations were identified. Moreover, we found some unique features of ABCC8 gene mutations in southern Chinese CHI patients with more novel and common mutations.The deletion/insertion mutation c.3224-3226delACC ins CAGCCAGGAACTG was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five compound heterozygous mutations of ABCC8 gene were identified in this study, and three of them were diazoxide-responsive. Forty patients were diazoxide-responsive, 13 patients were diazoxide-unresponsive and 12 patients received dietary treatment only. A pancreatectomy was performed in 10 patients who were unresponsive to medical treatment.

Conclusion:

To the best of our knowledge, this is the first study of CHI in south China. Mutations in ABCC8 are the most common causes of CHI in this cohort. Diazoxide and dietary treatment were effective in most patients. Multicentre studies are necessary to obtain the long-term follow-up characteristics of such patients at the national level.

Keywords: Congenital hyperinsulinism, Clinical management, Gene mutation