A case series of maturity-onset diabetes of the young highlighting atypical presentations and the implications of genetic diagnosis.

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic diabetes characterized by onset at a young age and an autosomal dominant mode of inheritance. Notably, MODY accounts for 2%-5% of all diabetes cases, and its distinction from types 1 (T1DM) and 2 (T2DM) diabetes mellitus is often challenging. We report herein the cases of two girls and a boy who presented initially with diabetic ketoacidosis.

Clinical Profile and Efficacy of Long-Acting Octreotide in Hyperinsulinemic Hypoglycaemia.

Introduction: Hyperinsulinemic hypoglycaemia (HH) is characterised by unregulated insulin secretion, leading to persistent non-ketotic hypoglycaemia with a lack of alternate fuel that induces a severe risk for brain damage and neurodevelopmental abnormalities. Octreotide, a somatostatin analogue, has been effectively administered as subcutaneous injections or depot preparations in diazoxide-unresponsive HH.

Methods: Children and infants with HH receiving short-acting octreotide injections were included.

Nutritional Status of Underprivileged Indian Children and Youth with Type-1 Diabetes - A Multicentre Study.

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability.

Use of Continuous Glucose Monitoring System in Children with Type 1 Diabetes Mellitus in a Resource Limited Setting.

Background: Regular self-monitoring of blood glucose (SMBG) remains the mainstay method for diabetes monitoring. The major limitation of SMBG is poor compliance and it only provides a snapshot of glucose values at that point of time. Continuous glucose monitors (CGMs) are non-invasive devices which measure subcutaneous interstitial glucose for every five minutes and provide glucose variability throughout the day.

Van Wyk Grumbach Syndrome and Ovarian Hyperstimulation in Juvenile Primary Hypothyroidism: Lessons From a 30-Case Cohort.

Context: Prolonged hypothyroidism in children commonly causes short stature with delayed bone maturation, and delayed puberty. However, a paradoxical occurrence of peripheral precocious puberty and pituitary enlargement in chronically untreated juvenile hypothyroidism was first reported by Van Wyk and Grumbach in 1960.

Objective: To create increased awareness and a better understanding of this clinical entity among emergency room physicians, pediatricians, surgeons, gynecologists and oncologists.

Clinical Experience from a Single Tertiary Care Center: Neonatal Diabetes Mellitus with Multiple Epiphyseal Dysplasia-Wolcott-Rallison's Syndrome.

Wolcott-Rallison's syndrome (WRS) is a rare nonautoimmune autosomal recessive disorder characterized by neonatal diabetes mellitus, epiphyseal dysplasia, and growth retardation. This is the most common cause of diabetes mellitus in patients with consanguineous parents. WRS is distinguished from other types of neonatal or early-onset diabetes by clinical characteristics and genetic testing.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

Background: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country.

Clinical, radiological and molecular studies in 24 individuals with Dyggve-Melchior-Clausen dysplasia and Smith-McCort dysplasia from India.

Background: Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondyloepimetaphyseal dysplasias with identical radiological findings. The presence of intellectual disability in DMC and normal intellect in SMC differentiates the two. DMC and SMC1 are allelic and caused by homozygous or compound heterozygous variants in .

Optimizing Cord Blood Thyroid Stimulating Hormone Cutoff for Screening of Congenital Hypothyroidism-Experience from Screening 164,000 Newborns in a Tertiary Hospital in India.

Background And Objectives: In our institution, we have an ongoing newborn thyroid screening (NBS) program since July 2001. In the initial 9 months, we used cord blood thyroid-stimulating hormone (TSH) (CBTSH) cutoff of 20 mIU/L and thereafter the cutoff was increased to 25 mIU/L. Our objective was to evaluate whether a CBTSH cutoff of 25 mIU/L is sensitive and cost-effective in NBS of congenital hypothyroidism (CH).

WFS1 Gene-associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India.

Context: Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge.

Objective: With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes.

Insulin gene mutations linked to permanent neonatal diabetes mellitus in Indian population.

Background And Aim: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations.

Methods: Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM.

Genotype-phenotype correlation of K channel gene defects causing permanent neonatal diabetes in Indian patients.

Background: There are very few reports pertaining to Indian patients with neonatal diabetes mellitus (NDM). Activating or gain of function mutations of K channel genes namely KCNJ11 and ABCC8 are most predominant cause of permanent neonatal diabetes mellitus (PNDM).

Objectives: To identify the genotype-phenotype correlation of K channel gene defects in a large series of (n = 181) Indian PNDM patients.

Severe Familial Hypertriglyceridemia: Successful Treatment With Insulin and a Modified Meal Plan.

Context: Mutations in genes encoding the lipoprotein lipase enzyme, its cofactor, or transport proteins can cause severe familial hypertriglyceridemia, resulting in serious complications, such as severe pancreatitis, hepatosplenomegaly, lipid encephalopathy, and failure to thrive. Current treatment includes a low-saturated-fat formula enriched with high medium-chain triglyceride (TGs), oral fibrates, omega-3 fatty acids, or plasmapheresis.

Case Description: A 71-day-old infant with very severe hypertriglyceridemia and recurrent pancreatitis associated with a likely pathogenic variant in the gene was treated successfully with insulin infusion and a locally prepared low-fat formula feed after stopping breast milk.

Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

Introduction: Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression.

Case Report: We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%.

Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians.

Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India.

Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.

Background: A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus.

Glucose tolerance, insulin resistance and insulin secretion in young south Indian adults: Relationships to parental size, neonatal size and childhood body mass index.

Objective: To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.

Research Design And Methods: 2218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages.

Community effect of Haemophilus influenzae type b vaccination in India.

We assessed the effect of distribution of Haemophilus influenzae type b (Hib) vaccine in the private health care sector on Hib meningitis admissions at a referral hospital in India. The annual mean number of Hib cases was 10.7 before Hib vaccine introduction, falling to 3.

High prevalence of glucose intolerance even among young adults in south India.

India is experiencing an epidemic of Type 2 diabetes mellitus (DM) in young adults. This study reports the prevalence of glucose intolerance, and insulin profiles, and their relationship to lifestyle factors in 2218 young adults (aged 26-32 years; 997 urban, 1221 rural) in south India. They were drawn from a cohort of 10,691 individuals born during 1969-1973 in Vellore and nearby villages.