ESPE Abstracts

Background: Automimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an extremely rare autoimmune condition caused by AIRE (autoimmune regulator) gene mutations and characterised by a classic triad of 1) chronic mucocutaneous candidiasis, 2) hypoparathyroidism and 3) adrenal insufficiency. APECED can involve any endocrine or non-endocrine organ. Consequently, clinicians need to be mindful of the great variability in presentation. Although ad...

Background: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia when paternally inherited. Mutations on the paternal, but not the maternal, GNAS allele are associated with intrauterine growth retardation (IUGR). Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2–13 (including XL and Gαs) than with exo...

Background: GNAS gene is a complex imprinted locus, resulting in the expression of at least four transcripts (XL, NESP55, A/B and Gsα) characterized by their specific exon 1 and common exons 2-13. While Gαs is biallelically expressed in most tissues, XL is only expressed from the paternal allele. Maternally inherited, loss-of-function mutations affecting those GNAS exons that ...

Background: Subclinical hypothyroidism (SH) is defined as normal tyrosine levels in the presence of TSH concentrations between 5 and 10 mU/ml. The impact of SH on IGF system and growth of infants remains unknown.Objective and hypotheses: To evaluate IGF1, IGFBP3 levels and growth velocity (GV) of infants with SH.Method: 98 children up to 36 months of age, recalled due to a TSH >5 mU/ml in the neonatal screening test, were divid...

Introduction: Androgens are essential for the development of male sex characteristics. Testosterone (T) production from androstenedione (A) by the Hydroxysteroid 17-Beta Dehydrogenase 3 (HSD17B3) in gonadal Leydig cells triggers the differentiation of the Wolffian ducts into epididymis, vas deferens, seminal vesicles and the prostate. Shortly after, the virilisation of the external male genitalia starts through the conversion of T into dihydrotestosterone (DHT...

Background: Folate and cobalamin are needed for synthesis of methionine, a substrate of methylation in epigenetic, and epigenomic pathways. Methyl donor deficiency (MDD) leads to hyperhomocysteinemia, which has been related to osteoporosis in humans and disruption of epiphyseal cartilage and bone development in rodents. Recent studies have revealed evidence for association between 25(OH)D3 and homocysteine levels, however, underlying mechanisms remain elusive.<p...

Background: Growth in infancy is considered primarily to be regulated by nutrition and insulin, whereas less is known about the influence of IGF-I, reproductive hormones and other factors of importance. Recently, paternally inherited genetic defects of DLK1 (Delta-like 1 homolog) were found in girls with central precocious puberty (CPP) with a metabolic phenotype. In addition, low maternal serum DLK1 concentrations were significantly lower in pregnant women wh...

Introduction: PTEN hamartoma tumor syndrome (PHTS) is a rare genetic disorder caused by germline mutations in the tumor suppressor gene Phosphatase and tensin homologue (PTEN), a negative regulator of the phosphoinositide-3 kinase (PI3K)/AKT/ mechanistic target of rapamycin (mTOR) pathway. Children with PHTS frequently develop adipose tissue overgrowth, so called lipomas that can lead to loss of organ function due to displacing lipoma growth. Currently, except...

Pro-opiomelanocortin (POMC) and the melanocortin-4-receptor (MC4R) are playing a key role within the leptin-melanocortin-pathway and thereby for satiety regulation. Mutations within these genes are leading to hyperphagia and early-onset obesity. However, observations of cardiac abnormalities including left ventricular dilatation and reduced contractibility in the MC4R knockout mouse model and reports about a reduced blood pressure in human MC4R variant carriers, led us to inve...

Background and Aims: Thyroid hormones profoundly affect energy metabolism but their interrelation with food preference, which might contribute to childhood obesity development, are much less understood. Here we investigated if age-related changes of thyroid hormone levels are paralleled by specific modulation of food preference and potentially linked to the level of obesity in children and adolescents.Patients and Methods:</stron...