The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism

Objective In children with congenital hyperinsulinism (CHI), K ATP channel genes ( ABCC8 and KCNJ11 ) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI. Design Follow-up observational study at two CHI referral hospitals. Methods Clinical outcomes such as subtotal pancreatectomy, 18 F-Dopa positron emission tomography–computed tomography (PET–CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI. Results In total, 32 (32%) children had pathogenic mutations in K ATP channel genes (27 in ABCC8 and five in KCNJ11 ), of which 11 (34%) were novel. In those negative at initial screening, other mutations ( GLUD1 , GCK , and HNF4A ) were identified in three children. Those with homozygous/compound heterozygous ABCC8 / KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with 18 F-Dopa PET–CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy. Conclusions Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require 18 F-Dopa PET–CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.