Heterozygous Insulin Receptor Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series.

Mutations in the gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment.

Maternal attitude towards delaying puberty in girls with and without a disability: a questionnaire-based study from the United Arab Emirates.

Background: Parental anxiety about the impact of puberty/menses, particularly in girls with severe disability leads to seeking therapeutic pubertal suppression. We aim to explore maternal attitudes and reasons for seeking pubertal suppression.

Methods: Mothers of girls receiving gonadotropin -releasing hormone analogue therapy in Mafraq hospital, Abu Dhabi were enrolled in the study.

Retrospective review of Synacthen testing in infants.

Background: A subnormal cortisol response (30 min level (C)<550 nmol/L) to synthetic adrenocorticotrophic hormone/Synacthen test (SDST) in all infants does not necessarily indicate underlying or persistent hypothalamic-pituitary-adrenal axis pathology.

Methods: We retrospectively evaluated the diagnoses and outcomes in 68 infants who had a SDST at age <6 months from 2011 to 2014.

Results: 29 (43%) infants had a subnormal SDST.

The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres.

Objectives: The management of paediatric craniopharyngiomas was traditionally complete resection (CR), with better reported tumour control compared to that by partial resection (PR) or limited surgery (LS). The subsequent shift towards hypothalamic sparing, conservative surgery with adjuvant radiotherapy (RT) to any residual tumour aimed at reducing neuroendocrine morbidity, has not been systematically studied. Hence, we reviewed the sequelae of differing management strategies in paediatric craniopharyngioma across three UK tertiary centres over four decades.

Acceptance of a reusable self-injection device for recombinant human growth hormone: final data from a questionnaire-based, cross-sectional, international, multicenter, observational study in pediatric patients.

Background: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePal™) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope(®) within routine clinical practice.

Methods: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope(®) (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePal™, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients).

Feeding Problems Are Persistent in Children with Severe Congenital Hyperinsulinism.

Background: Congenital hyperinsulinism (CHI) is a rare but severe disorder of hypoglycemia in children, often complicated by brain injury. In CHI, the long-term prevention of hypoglycemia is dependent on reliable enteral intake of glucose. However, feeding problems (FPs) often impede oral glucose delivery, thereby complicating the management of hypoglycemia.

Acceptability of the reusable SurePal™ self-injection device for Omnitrope(®) among pediatric patients: results from a questionnaire-based, cross-sectional, multicenter observational study.

Background: SurePal™ is a reusable self-injection system that has been developed to support daily administration of Omnitrope(®) (Sandoz, Kundl, Austria). A questionnaire-based cross-sectional survey was conducted to evaluate acceptability of, and preference for, SurePal™ in pediatric patients who were prescribed treatment with Omnitrope(®) within routine clinical care.

Methods: This multicenter, observational study was incorporated into the ongoing non-interventional PATRO (PAtients TReated with Omnitrope(®)) Children study.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects.

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3.

Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot Trial with MaxEPA(R.).

Objective: Congenital hyperinsulinism (CHI) is a rare condition of hypoglycemia where therapeutic options are limited and often complicated by side-effects. Omega-3-polyunsaturated fatty acids (PUFA), which can suppress cardiac myocyte electrical activity, may also reduce ion channel activity in insulin-secreting cells. PUFA supplements in combination with standard medical treatment may improve glucose profile and may reduce glycemic variability in diazoxide-responsive CHI.

Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism.

Introduction: Neuroglycopenia is recognized to be associated with abnormal neurodevelopmental outcomes in 26-44% of children with persistent congenital hyperinsulinism (P-CHI). The prevalence of abnormal neurodevelopment in transient CHI (T-CHI) is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI.

The association of cardiac ventricular hypertrophy with congenital hyperinsulinism.

Objective: Ventricular hypertrophy (VH) has been observed in children with congenital hyperinsulinism (CHI), a condition of hypoglycaemia characterised by dysregulated insulin secretion, but the prevalence is not known.

Patients And Methods: Cardiac assessment was performed in children (n=49) with CHI at diagnosis and follow-up. Two dimensional and Doppler echocardiography studies were used to assess cardiac structures, while M-mode study was used to measure left ventricular (LV) dimensions, subsequently converted to Z scores.

Persistent Müllerian duct syndrome: lessons learned from managing a series of eight patients over a 10-year period and review of literature regarding malignant risk from the Müllerian remnants.

Unlabelled: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Approximately 200 cases of persistent Müllerian duct syndrome have been reported over the last 50 years and most authors suggest leaving the Müllerian remnant in situ because of the difficulty in dissection and the presumed absence of risk of malignancy. However, with increasing reports of Müllerian malignancies emerging, we report our 10-year experience of managing patients with persistent Müllerian duct syndrome, with removal of müllerian remnants.

An observational study of type 2 diabetes within a large Australian tertiary hospital pediatric diabetes service.

Background: Type 2 diabetes mellitus (T2DM) is emerging as a significant clinical problem within the pediatric population.

Objective: The objective of this study was to identify patients with T2DM in a large tertiary hospital diabetes service and examine aspects relating to clinical course and management.

Methods: An initial audit of our diabetes service (over 6 yr) was followed by a 2-yr period of prospective case ascertainment to identify patients with T2DM.

Three siblings with self-resolving congenital hyperthyrotropinaemia secondary to thyrotropin receptor blocking antibodies.

Thyrotropin receptor blocking antibodies are a rare cause of hyperthyrotropinaemia and more rarely of congenital hypothyroidism. We report a case of hyperthyrotropinaemia but normal thyroid hormone in the newborn of a mother with hypothyroidism treated with thyroxine. Two older siblings had similar high thyrotropin and normal thyroid function in the newborn period which did not require hormone treatment and resolved spontaneously.

Ethnic differences in insulin resistance and body composition in United Kingdom adolescents.

Context: Type 2 diabetes is increasingly recognized in childhood, occurring more frequently in the United Kingdom in South Asians and in girls. South Asian children have been shown to be more insulin resistant than white European children, and girls more insulin resistant than boys. It is not clear how these sex and ethnic differences relate to body composition in childhood.

The emergence of type 2 diabetes in childhood.

Type 1 diabetes (with predominant insulin deficiency) was until recently assumed to be the diagnosis of almost all children presenting with glucose intolerance. This requires insulin treatment via subcutaneous injections, and most patients develop microvascular and macrovascular complications in adulthood. Advances in genetics in the 1990s identified a group of genetic disorders of pancreatic beta-cell function (maturity-onset diabetes of the young) for which the outlook is better than type 1, genetic testing is available, and oral medication is the preferred treatment.

Childhood idiopathic chondrolysis of the hip: MRI features.

Background: Childhood idiopathic chondrolysis of the hip (ICH) causes progressive destruction of the articular cartilage of the hip joint with associated bone remodelling. The MRI features of this disease have not previously been described.

Objective: To document the MRI features of childhood ICH and determine which features may help distinguish ICH from other causes of hip joint destruction in the paediatric population.