Birth prevalence and characterisation of congenital hyperinsulinism in Western Australia over two decades
Adam J Stafford-Bell1, Amanda J Hooper2, Rachel Romans1
1Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, WA, Australia.
Insights
Congenital hyperinsulinism (CHI) affects 1 in 17,394 newborns in Western Australia, with genetic factors playing a key role. Early genetic evaluation in newborns with CHI contributes to a higher observed prevalence.
Area of Science:
- Medical Genetics
- Paediatric Endocrinology
- Metabolic Disorders
Background:
- Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by persistent hypoglycemia due to unregulated insulin secretion.
- Understanding the prevalence, genetic basis, and clinical management of CHI is crucial for improving patient outcomes.
Purpose of the Study:
- To determine the birth prevalence of congenital hyperinsulinism (CHI) in Western Australia (WA).
- To characterize the genotype, phenotype, and management strategies for children diagnosed with CHI in WA.
- To investigate the impact of early genetic evaluation on CHI prevalence and management.
Main Methods:
- A population-based retrospective study was conducted from 2005 to 2024 at WA's tertiary pediatric center.
- Exclusion criteria included transient perinatal stress-induced hyperinsulinism (HI) and insulinoma.
- Data collected encompassed clinical presentation, diagnostic investigations, and treatment modalities.
Main Results:
- The birth prevalence of CHI was found to be 1 in 17,394 live births.
- Of 40 identified cases, 65% presented neonatally, with 32.5% symptomatic and 15% experiencing seizures.
- Genetic etiology was identified in 80% of cases, with K-ATP channel defects (ABCC8, KCNJ11) being the most common.
- 80% of patients responded to medical therapy; 20% required surgical intervention, and 6 patients developed secondary diabetes post-pancreatectomy.
Conclusions:
- The higher prevalence of CHI in WA compared to European populations may be attributed to early genetic screening of newborns.
- Genotype-phenotype correlations align with existing literature, underscoring the importance of genetic investigation for guiding CHI management.
- Genetic analysis in infants with CHI is vital for informing appropriate clinical strategies and improving outcomes.
Objectives:
To describe the birth prevalence and characterise the genotype, phenotype and management of children with congenital hyperinsulinism (CHI) in Western Australia (WA).
Methods:
A population-based retrospective study (2005-2024) of children with CHI was conducted at the tertiary paediatric centre in WA. Children with transient perinatal stress-induced HI and insulinoma were excluded. Data collection included clinical presentation, investigations and management.
Results:
The birth prevalence was 1 in 17,394 per 100,000 live births. Of 40 CHI cases, 65 % were neonatal presentations. 32.5 % were symptomatic with seizures in 15 % of presentations. An aetiology was identified in 80 % (n=32); 64.5 % (n=21) had identified pathogenic gene variants with K-ATP channel defects in 14 children [ABCC8 (n=11), KCNJ11 (n=3)], the remainder had syndromic HI (n=11). 80 % (n=32) responded to medical therapies; 78 % (n=25) had an identified etiology. A pathogenic variant was identified in six of the seven infants with CHI which resolved in six months. Of those children who were diazoxide unresponsive (n=10), two stabilised on octreotide while eight (20 %) required surgical management, which was curative in focal lesions (n=2). Secondary diabetes post pancreatectomy (n=6) occurred at a mean age of 5.25 years. The cohort had high continuous glucose monitoring uptake (92 %) for glucose monitoring following subsidy with nine commenced in the neonatal period.
Conclusions:
The prevalence of CHI in WA is higher than the reported European-ancestry population due to early genetic evaluation of newborns with CHI. Correlation between genotype and phenotype is consistent with literature and supports genetic investigation of infants with CHI to inform management.
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