Rajni Sharma1, Kakali Roy1, Amit Kumar Satapathy2, Anil Kumar1, Pamali Mahasweta Nanda1, Nishikant Damle3, Jayne A L Houghton4, Sarah E Flanagan5, Venkatesan Radha6, Viswanathan Mohan6, Vandana Jain7. 1. Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 2. Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Orissa, India. 3. Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India. 4. Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK. 5. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK. 6. Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India. 7. Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Prof Vandana Jain, Division of Pediatric Endocrinology, Room no.3058, Teaching Block, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029. drvandanajain@gmail.com.
Abstract
BACKGROUND: There is limited data from India regarding medical management of congenital hyperinsulinism (CHI). OBJECTIVE: To study the molecular diagnosis, medical management and outcomes of children with CHI. STUDY DESIGN: Ambispective. PARTICIPANTS: Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital. OUTCOMES: Clinical and genetic profile, treatment, and response. RESULTS: 42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxide-responsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed. CONCLUSIONS: Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.
BACKGROUND: There is limited data from India regarding medical management of congenital hyperinsulinism (CHI). OBJECTIVE: To study the molecular diagnosis, medical management and outcomes of children with CHI. STUDY DESIGN: Ambispective. PARTICIPANTS: Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital. OUTCOMES: Clinical and genetic profile, treatment, and response. RESULTS: 42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxide-responsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed. CONCLUSIONS: Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.
Authors: Ved Bhushan Arya; Senthil Senniappan; Huseyin Demirbilek; Syeda Alam; Sarah E Flanagan; Sian Ellard; Khalid Hussain Journal: PLoS One Date: 2014-05-19 Impact factor: 3.240