ESPE Abstracts

Objective: Merge and standardize the scarce data on molecular and phenotypic findings of mutations in the human leptin receptor (LEPR) gene causing a rare form of severe early-onset obesity.Methods: We summarized functional and phenotypic traits of LEPR mutations reported in the literature in a structured and comprehensive manner. Additional data was obtained from 6 subjects of our outpatient clinic not reported so far. Functionality of mutations was ass...

Background: Pituitary adenomas secreting GH rarely present in childhood. We report the clinical features, management and outcome of the 5 cases referred to a tertiary Paediatric Endocrine/Neurosurgical service over a 20-year period.Patients: **4 Male:1 Female - all aged 15 years at referral. Tanner puberty stages G3-5; B3. Clinical follow-up data range 2 months – 8 years.Clinical features at presentation: Headache, n=...

Background: That mortality is not increased in rhGH-treated patients when adjusting for birth characteristics was recently published (1). When applying a developed mortality model of the general population, the observed and expected deaths in rhGH-treated IGHD, ISS and SGA patients (n=3847) where 21 and 21.99, respectively. The model includes gender, age, calendar year, gestational age (GA), birth lengthSDS (BLSDS), birth weightSDS (BW...

Background: Depending on age, needs and preferences in insulin therapy strongly differ between children and adolescents with type 1 diabetes (T1D).Objective and hypotheses: To analyse trends in insulin regimen and type of insulin used over the last two decades in three age-groups of pediatric patients with T1D from Germany/Austria.Method: 63 967 subjects (<18 year of age) with T1D documented between 1995 and 2014 from the &#145...

Background: Mutations in more than 20 genes are described to cause monogenic diabetes. Nevertheless, numerous families with diabetes of unknown ethology and suspected genetic defect have no molecular diagnosis. This not only impedes our understanding of disease mechanisms but also prevents from predicting the clinical course of the patients and applying the pathogenesis-oriented treatment.Objective: To identify novel gene(s), causing monogenic adolescent...

Background: Studies in animal models revealed that brown and white adipocytes derive from different progenitor cells. Molecular characteristics of these cells have not been investigated in detail in humans.Objective and hypotheses: To identify novel markers of human brown adipocyte progenitor cells.Method: Progenitor cells from human paired deep neck and subcutaneous adipose tissue samples were obtained from n=12 subjects ...

Background: Hereditary hypophosphatemic rickets (HHR) is a rare genetic disease characterized by renal phosphate wasting, caused by elevated circulating FGF23. Despite the current available treatment complications include short stature, hyperparathyroidism, pseudofractures, bone pain, bone demineralization and osteoporosis, nephrocalcinosis and enthesopathies. Elevated circulating FGF23 was recently involved in glucose metabolism and cardiovascular function.<p class="abste...

Background: Pancreas aplasia (PA) and neonatal diabetes mellitus (NDM) syndrome is a rare disease that usually presents in the 1st months of life.Objective and hypotheses: We aimed to characterize molecular genetic defects in a cohort of six NDM/PA patients with up-to-date unknown pathogenesis with optimum genetic testing.Method: As part of our ESPE-RU-project ‘Understanding the molecular basis of diabetes mellitus associated ...

Background: Early-onset severe obesity due to leptin deficiency typically results from a defect of leptin production or secretion due to mutations in the leptin gene. Recently we described a new form of leptin deficiency caused by bioinactivity of the hormone and associated with high circulating leptin levels (New England Journal of Medicine 2015 372 48–54).Method: Serum leptin was measured by ELISA. The leptin gene was seq...

Here we identified and characterized a heterozygous tandem duplication at the ASIP (agouti-signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female index patient with extreme childhood obesity. In patient-derived adipose tissue samples, we observed pronounced differentiation of stroma-vascular fraction (SVF) cells into adipocytes in the patient compared to normal control cells. We further found reduced mitochondrial maximum respir...