IMPE Abstracts

Congenital Hyperinsulinism (CHI), a heterogenous complex disorder, is the commonest cause of refractory hypoglycaemia in infants. The treatment of diazoxide-unresponsive CHI is a major challenge in clinical practice.

Objective: To study the clinical profile, molecular characterisation, response to long acting octreotide analogue (LAR) therapy and short term outcome in diazoxide unresponsive CHI presenting to our Centre.

Method: Retrospective review of records of children with diazoxide-unresponsive CHI who were treated with monthly injections of long-acting octreotide analogue (LAR). Demographic profile, clinical presentation, mutation characteristics and treatment details were recorded. Follow up details in terms of growth characteristics, sugar control was assessed to determine the efficacy and side effects of the treatment.

Results: Fifteen children (11 girls, 1 pair of siblings) with diazoxide unresponsive CHI on injection LAR were studied. The median age at diagnosis was 2months (range, 4days to 20months) and median age at last follow up 2.5years (range, 1 to 7.6 years). Eight were born of consanguineous marriage. One child was referred post pancreatectomy. Mutation analysis was done in all and revealed KCNJ11 homozygous mutation in 3, KCNJ11 heterozygous mutation in 1, ABCC8 homozygous mutation in 5, ABCC8 heterozygous mutation in 6 cases. LAR was started at a median age of 9 month (range, 3 to 24months) at a maximum dose of 19.8±9.3µg/kg/day. LAR along with carbohydrate rich feeding and regular home monitoring of glucose effectively maintained sugar levels in all patients. One child with ABCC8 heterozygous paternally inherited mutation, LAR could be stopped at 4year 9 months age. In two children with similar mutation the LAR dose requirement has markedly reduced over a follow up period of 3 years and 7 years respectively. None of the children had elevation of liver enzymes and transient asymptomatic gallbladder pathology occurred in three cases. Height SDS at last follow up was -1.2±1.01. Three children with normal IGF1, were faltering in growth which was attributed to poor nutritional status, refractory anaemia and exocrine pancreatic insufficiency. On follow up, 11 (78%) children had normal neurodevelopmental outcome, 2(14%) had epilepsy and 1(7%) child was diagnosed as autism spectrum disorder. One child was lost to follow up.

Conclusion: Long acting octreotide analogue is an effective form of alternative therapy in diazoxide unresponsive CHI. Further long term follow-up studies are needed to prove their safety and efficacy.