ESPE Abstracts

Introduction: Beta-thalassaemia is caused by point mutations leading to decreased production of beta-globin, which results in defective red blood cells and ineffective erythropoiesis. Complications are microcytic hypochromic anaemia, extramedullary haematopoiesis and increased intestinal iron absorption due to compensation mechanisms. The resulting iron overload can be aggravated by recurrent blood transfusions necessary for treatment of anaemia and may cause several endocrine...

Background: The adrenocorticotropic hormone (ACTH) is a 39 amino acid polypeptide secreted by the anterior pituitary and regulates cortisol secretion from the adrenal cortex. Cortisol has negative feedback and regulates the synthesis and secretion of the ACTH. Excess ACTH is associated with a wide range of diseases including congenital adrenal hyperplasia (CAH). Classic CAH due to the 21-hydroxylase (CYP21A2) deficiency causes a reduction or loss of cortisol synthesis. Here th...

Objectives: Deficiency of the short stature homeobox-containing (SHOX) gene is a potential etiology of short stature in children. The phenotypic spectrum of SHOX deficiency disorders, caused by haploinsufficiency of the SHOX-gene and inherited in a pseudo-autosomal dominant manner, is highly variable, even within the same family, ranging from nonspecific short stature to Leri-Weill dyschondrosteosis (LWD). Short stature, mesomelia and Madelung deformity define the classic clin...

Background: Transient neonatal adrenal dysfunction is reported in association with antiretroviral therapy with Lopinavir and Ritonavir. Other drugs have not been tested.Objective and hypotheses: We report on a preterm girl, born 26 weeks gestation, with elevated 17-hydroxyprogesterone (17OHP) at newborn screening. During pregnancy the mother was treated for HIV with Atripla (Efavirenz, Tenofovir, Emtricitabin) and viral load was suppressed. Furthermore t...

Background: 3β-Hydroxysteroiddehydrogenase (3β-HSD) is a key enzyme in steroidogenesis, responsible for the conversion of Δ5- to Δ4-steroids. Deficiency in 3β-HSD results in congenital adrenal hyperplasia (CAH). The molecular etiology of 3β-HSD deficiency lies in a defect in HSD3B2 gene.Clinical case: A healthy newborn girl was admitted on day of life (DOL) 8 due to increased 17-OH-progesterone (17OHP) in newborn sc...

Background: Isolated GH deficiency type II (IGHD II), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human GH (hGH) gene (GH-1). These mutations, occurring in and around exon 3, cause complete exon 3 skipping and produce a dominant-negative 17.5-kDa GH isoform that reduces the accumulation and secretion of wt-GH.Objective and hypotheses: As the severity of IGHD II inversely correlate...

Background: Androgens are steroid hormones necessary for human sex development. Testosterone (T) and the more potent dihydrotestosterone (DHT) are maybe the best known androgens, which exert their effect by binding and activating the androgen receptor. Steroid reductases 5α (SRD5As) catalyse the conversion of T to DHT in the classic androgen production pathway, or from 17-hydroxyprogesterone to 17OH-dihydroprogesterone, and androstenedione to androstanedione in alternate ...

Background: CYP27B1 converts 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3, playing a vital role in calcium homeostasis and bone growth. Vitamin D-dependent rickets type 1 (VDDR-1) is a rare autosomal recessive disorder caused by mutations in CYP27B1.Objective and hypotheses: Enzymatic and structural analysis of mutations in a patient with calcipenic rickets.Method: Two siblings presented with calcip...

Background: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature.Objective and hypotheses: We report on a girl referred for assessment of short stature (−4.6 SDS) at a chronological age of 7 yr 10 mo. The GH deficiency was confirmed by standard GH provocation tests, which revealed severely reduced GH and IGF-I concentration...

Background: Butyrate is a short-chain fatty acid closely related to the ketone body β-hydroxybutyrate (BHB) considered as the major source of energy during prolonged exercise. During fasting, when the liver switches to fatty acid oxidation, a rise in serum GH occurs concomitantly with the accumulation of BHB and short chain fatty acids (SCFA) acetate, propionate and butyrate. Interactions between GH, ketone body and SCFA during the metabolic adaptation to fasting are poor...