Hyperamylasaemia in paediatric inflammatory bowel disease: Aetiology, outcomes and genetic determinants

OBJECTIVES: A subset of patients with inflammatory bowel disease (IBD) develop hyperamylasaemia. This study examines its causes, clinical outcomes and the impact of amylase gene copy number variation (CNV) using whole exome sequencing (WES). METHODS: We retrospectively analysed 334 patients with paediatric IBD (≤18 years, diagnosed 2015-2022) who were recruited to the Genetics of IBD Study-University Hospital Southampton. Patients with amylase levels above the laboratory's reference range (102 U/L) were identified, clinically characterised and followed for ≥2 years. Amylase gene CNV was estimated and correlated with serum amylase levels. Findings were replicated in an additional cohort of 554 paediatric and adult patients. RESULTS: Hyperamylasaemia was found in 62/334 patients (18.6%), with 29% of these presenting at diagnosis. It was significantly associated with younger age at diagnosis (p = 0.044), non-European ethnicity (p = 0.013) and body mass index (BMI) > 91st centile (p = 0.0467). Hyperamylasaemia resolved in 77% of patients; in the majority (85%), spontaneously and in the remainder after medication withdrawal. One patient developed acute pancreatitis; another with ansa pancreatica had recurrent pancreatitis. Although AMY mean gene read counts positively correlated with median serum amylase levels in both cohorts (Primary pIBD cohort, p < 0.0001 for both AMY1 & AMY2; Replication cohort, p < 0.0001 for AMY1 & p = 0.0017 for AMY2), they explained <10% of the variance in amylase levels. CONCLUSIONS: Hyperamylasaemia is common in pIBD, associated with younger age, non-European ethnicity and higher BMI. Most cases are benign and self-limiting. Our findings confirm a strong association between elevated amylase and additional copies of AMY genes.