Molecular Characterization and Management of Congenital Hyperinsulinism: A Tertiary Centre Experience

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 diazoxideresponsive. 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.

Clinical Profile and Outcome of Infantile Onset Diabetes Mellitus in Southern India.

Objective: To study the etiology, clinical presentation and outcome of infantile onset diabetes mellitus (IODM). Design: Descriptive cohort study. Retrospective study from 1999- 2007 and prospective from 2008-2012. Setting: The diabetic clinic at a Pediatric tertiary care referral institute in Chennai. Methods: All infants diagnosed to have diabetes at less than one year of age were studied. Study variables were age at onset, gender, mode of presentation, birth weight, initial blood glucose, serum HbA1c, serum c–peptide levels, outcome at initial presentation, insulin requirement, associated co-morbid conditions, genetic analysis and outcome at the end of the study or until they were followed up. Results: 40 infants with infantile onset diabetes were studied, constituting 8% of all children with onset of DM at less than 12 years of age. 67.5% of these children presented with diabetic keto acidosis (DKA), only 30% had a provisional diagnosis of DM or DKA at first physician contact. 63% of IODM with onset less than 6 months and 30% with onset more than 6 months were of low birth weight. Nearly 85% of the study group had low C-peptide levels. 84.5% of IODM with onset less than 6 months and 55% of those with onset more than 6 months were monogenic. Wolcott Rallison syndrome was the commonest type encountered. Genetic diagnosis aided switching over from insulin to oral sulphonylurea in 5 children with KCNJ11 and ABCC8 mutations. Missed diagnosis, recurrent admissions for metabolic instability and developmental delay were common problems in IODM. Mortality at 12.5 year follow up was 32.5%. Conclusions: IODM with onset at less than 6 months is predominantly monogenic and low birth weight is more common. 55% of IODM were misdiagnosed at onset. Developmental delay is the common co morbid condition in IODM. Genetic diagnosis aids change of therapy to oral sulphonylurea.

Genes and diabetic retinopathy.

Several recent studies have provided evidence that good diabetes control is important to prevent diabetic retinopathy. However, some groups of patients develop diabetic retinopathy despite good control and others escape retinopathy despite poor control. This suggests the role of genetic factors in susceptibility to retinopathy. This article reviews the role of genetic factors in determining diabetic retinopathy.