Dataset Information

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

ABSTRACT: Objective:To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches. Methods:We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed 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 (25%) of the cohort, GLUD1 mutations were identified in five children, and no KCNJ11 or GCK mutations were identified. Moreover, some unique features of ABCC8 gene mutations in southern Chinese CHI patients were found in this study. The most common mutation was a deletion/insertion mutation p.Thr1042GlnfsX75 was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five novel ABCC8 mutations were detected. The mutations were p.Phe5SerfsX72, p.Gln273ArgfsX85, p.Leu724del, p.Asp1447Gly and IVS 25-1G>T. Five compound heterozygous mutations of ABCC8 gene were identified in this study, and three of these patients 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 a national level.

SUBMITTER: Xu A

PROVIDER: S-EPMC6878346 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Xu Aijing A Cheng Jing J Sheng Huiying H Wen Zhe Z Lin Yunting Y Zhou Zhihong Z Zeng Chunhua C Shao Yongxian Y Li Cuiling C Liu Li L Li Xiuzhen X

Journal of clinical research in pediatric endocrinology 20190618 4

<h4>Objective</h4>To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches.<h4>Methods</h4>We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed for <i>KCNJ11</i> and <i>ABCC8</i> genes. The <i>GLUD1</i> gene was sequenced in patients with hyperammonaemia. <i>GCK</i> gene sequencing was performed i ...[more]

PMID: 31208162

Similar Datasets

Project description:Background and aimsIn patients with congenital hyperinsulinism (CHI), recurrent hypoglycaemia can lead to longstanding neurological impairments. At present, glycaemic monitoring is with intermittent fingerprick blood glucose testing but this lacks utility to identify patterns and misses hypoglycaemic episodes between tests. Although continuous glucose monitoring (CGM) is well established in type 1 diabetes, its use has only been described in small studies in patients with CHI. In such studies, medical perspectives have been provided without fully considering the views of families using CGM. In this qualitative study, we aimed to explore families' experiences of using CGM in order to inform future clinical strategies for the management of CHI.MethodsTen patients with CHI in a specialist centre used CGM for twelve weeks. All were invited to participate. Semi-structured interviews were conducted with nine families in whom patient ages ranged between two and seventeen years. Transcripts of the audio-recorded interviews were analysed using an inductive thematic analysis method.ResultsAnalysis revealed five core themes: CGM's function as an educational tool; behavioural changes; positive experiences; negative experiences; and design improvements. Close monitoring and retrospective analysis of glucose trends allowed for enhanced understanding of factors that influenced glucose levels at various times of the day. Parents noted more hypoglycaemic episodes than previously encountered through fingerprick tests; this new knowledge prompted modification of daily routines to prevent and improve the management of hypoglycaemia. CGM use was viewed favourably as offering parental reassurance, reduced fingerprick tests and predictive warnings. However, families also reported unfavourable aspects of alarms and questionable accuracy at low glucose levels. Adolescents were frustrated by the short proximity range for data transmission resulting in the need to always carry a separate receiver. Overall, families were positive about the use of CGM but expected application to be tailored to their child's medical condition.ConclusionsPatients and families with CHI using CGM noticed trends in glucose levels which motivated behavioural changes to reduce hypoglycaemia with advantages outweighing disadvantages. They expected CHI-specific modifications to enhance utility. Future design of CGM should incorporate end users' opinions and experiences for optimal glycaemic monitoring of CHI.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets