Birth prevalence and characterisation of congenital hyperinsulinism in Western Australia over two decades

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.