ESPE Abstracts

Background: Pregnancy associated plasma protein (PAPP)-A2 is an insulin-like growth factor (IGF) binding protein (BP) protease that regulates IGF-1 availability, affecting postnatal growth. We have recently reported the first mutations in human PAPP-A2 causing short stature and changes in bone size and mineral density. However, the IGF system is involved in diverse physiological functions and to date it is unknown how mutations in PAPP-A2, which significantly reduce f...

Background: Obesity is a worldwide epidemic affecting adults and children. Social changes throughout history have contributed to modifications in nutrition and physical activity levels. These changes in lifestyle affected health, increasing the number of metabolic and cardiovascular diseases. Obese children already have a low grade systemic inflammation as well as markers of increased cardiovascular risk. The endothelial function is an important and early marker of atheroscler...

The growth hormone (GH)-insulin-like growth factor (IGF-1) system is essential for optimal human growth and energy homeostasis. Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a protease involved in the liberation of free IGF-1, leads to problems in growth and bone density in humans and mice. Patients with PAPP-A2 deficiency also present lower body mass and mild glucose intolerance. The present study aimed to determine the influence of 1 month of high carbohydr...

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a protease that regulates IGF-1 availability, causes postnatal growth failure and changes in bone size and density in humans and mice. The present study aimed to determine the effects of daily administration (from PND5 to PND35) of recombinant murine (rm) PAPP-A2, in comparison to rmGH and rmIGF1, on mouse auxology and bone microarchitecture in homozygous Pappa2 knock-out (ko/ko) mice of both sexes. Hormone treatm...

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a regulator of IGF-1 availability, causes postnatal growth failure in humans and mice, at least in part through dysregulation of bone size and density. The present study aimed to determine the effects of Pappa2 gene deletion and the response to recombinant murine IGF-1 (rmIGF-1) on femur microstructure and composition. Hydroxyapatite-related crystallography and ionic substitutions were analyzed by X-ray p...

Pregnancy associated plasma protein (PAPP)-A2 is an insulin-like growth factor (IGF) binding protein (BP) protease that regulates IGF-1 availability affecting postnatal growth. Mutations in human PAPP-A2 cause short stature and changes in bone size and mineral density. The present study aimed to characterize the effects of constitutive Pappa2 gene deletion on hypothalamic regulation of energy homeostasis in adult male and female mice. In addition to being sho...

Background: Genetic defects in NKX2.1 (chromosome 14q13) are associated with hypothyroidism, choreo-athetotic movements and respiratory distress, known as the “Brain-Lung-Thyroid syndrome”.Objective and hypotheses: To identify the genetic basis of a disorder compatible with the “NKX2.1 syndrome” and extra features outside the typical triad.Patients and methods: 10-year old girl with congenital ...

Background: Thyroid hormone resistance (THR) is a rare genetic disorder that may be caused by thyroid hormone (TH) cell transporter defects or metabolism defects, but most cases are caused by an inherited mutation in the TH receptor beta (THRB) gene. The reduced responsiveness of target tissues to TH is characterized by elevated TH and a normal or elevated thyroid-stimulating hormone (TSH) level. Differentiating between THR and TSH-producing pituitary...

Background: Cornelia de Lange (CdLS) syndrome (OMIM #122470) is a complex disease, characterized by distinctive facial features, failure to thrive, microcephaly, intrauterine growth retardation and anomalies in multiple organ systems. The complexity and severity of the endocrine commitment is variable. NIPBL, SMC1A, SMC3, RAD21 and HDAC8 genes, all involved in the cohesin pathway, have been identified to cause CdLS. There are few published studies on the endoc...

Introduction: CORNELIA DE LANGE Syndrome (CdLS) is a rare syndrome, first described in 1933 by the Dutch pediatrician CORNELIA DE LANGE. This syndrome represents a multi-systemic disorder with physical, cognitive and behavioral characteristics. It is evident in the typical or classical form (craniofacial appearance, short stature and limbs deformities). However, not all individuals with CdLS present with the classic phenotype, as the clinical presentation can ...