hrp0082fc2.1 | Bone & Mineral | ESPE2014

Asfotase Alfa: Sustained Improved Growth and Function with Extended Treatment in Children with Hypophosphatasia

Madson Katherine , Rockman-Greenberg Cheryl , Melian Agustin , Moseley Scott , Odrljin Tatjana , Reeves Amy , Whyte Michael

Introduction: Hypophosphatasia (HPP) is the rare, inherited, metabolic disease with broad-ranging severity caused by inactivating mutation(s) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. In the childhood form of HPP, there are mineralization defects of the bones and teeth, often with impaired physical function, muscle weakness, and decreased growth. We previously reported sustained radiographic improvement in rickets compared to historical controls in 5–1...

hrp0082fc2.2 | Bone & Mineral | ESPE2014

Hypophosphatasia: Gross Motor Function and Height Improvement in Infants and Young Children Treated with Asfotase Alfa for up to 3 Years

Bishop Nicholas , Simmons Jill , Lutz Richard , Odrljin Tatjana , Moseley Scott , Melian Agustin , Phillips Dawn , Whyte Michael

Introduction: Hypophosphatasia (HPP) is caused by inactivating mutation(s) within the gene for tissue nonspecific alkaline phosphatase (TNSALP). Patients with the perinatal and infantile forms of HPP suffer rickets, poor growth, and delayed gross motor function. In 2012, we detailed significant improvement in skeletal mineralization and respiratory function in such patients treated for 1 year with asfotase alfa, a bone-targeted recombinant human TNSALP,1 and recentl...

hrp0082fc12.6 | Obesity | ESPE2014

Resveratrol Inhibits Inflammation-Induced Production of Cytokines in Human Adipocytes

Zagotta Ivana , Killian Alexandra , Haas Jennifer , Kietzmann Thomas , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Background: Upon excessive expansion, adipose tissue is infiltrated by macrophages and shows increased production of inflammatory cytokines. This chronic low grade inflammation of adipose tissue is involved in the pathogenesis of insulin resistance. A supplementation with resveratrol can reverse the metabolic disturbances of human obesity, in part by mimicking the effects of caloric restriction.Objective and Hypotheses: We hypothesized that the beneficia...

hrp0082p1-d2-29 | Autoimmune Endocrine Disease | ESPE2014

Standard Population Screening for Diabetes Mellitus has Low Sensitivity in Identifying Diabetes in Adult Survivors of Childhood Bone Marrow Transplantation with Total Body Irradiation

Wei Christina , Unsworth Rebecca , Davis Nikki , Elson Ruth , Bradley Karin , Stevens Michael , Crowne Elizabeth

Background: Adult survivors of childhood leukaemia treated Bone marrow transplantation with total body irradiation (BMT/TBI) have an increased risk of diabetes mellitus (DM) disproportionate to their level of adiposity or other recognised risk factors. Post prandial hyperglycaemia due to reduced β-cell reserve after irradiation will be missed by fasting glucose (FG) levels. However, the UK National Institute of Clinical Excellence (NICE) screening guidelines recommend the...

hrp0082p1-d1-141 | Growth | ESPE2014

Whole Exome Sequencing is an Efficient Approach to Screen for Changes in Growth-Relevant Genes in Primary IGF1 Deficiency

Grosse Greta , Hilger Alina , Draaken Markus , Ludwig Michael , Reutter Heiko , Woelfle Joachim

Background: Primary IGF1 deficiency (PIGFD) is a rare disease defined by low IGF1 levels, GH sufficiency and absence of secondary causes of growth failure. Whereas some members of the GH–IGF axis have been shown to be implicated in the severe syndromic forms of PIGFD due to GH insensitivity, genetic causes of less severely affected patients are mostly unknown.Objective and hypotheses: The aim of the present study was to systematically investigate fr...

hrp0082p2-d3-492 | Endocrine Oncology | ESPE2014

Autoimmune Polyglandular Syndrome in a Patient with Tuberous Sclerosis

Stoppa-Vaucher Sophie , Elowe-Gruau Eglantine , Phan-Hug Franziska , Pitteloud Nelly , Hauschild Michael

Background: Tuberous sclerosis (TS) is an autosomal dominant neurocutaneous disorder involving many organ systems. The frequency of TS is around one per 5000 to 10 000 live births and is caused by mutation in the TSC1 or TSC2 genes. Autoimmune polyglandular syndrome type 2 (APS2) is an endocrinopathy characterized by two or more autoimmune diseases. Several susceptibility genes are known. The prevalence of APS2 is around 1:20 000.Object...

hrp0082p3-d1-817 | Growth | ESPE2014

Increased Required Dose of GH in Children with Inborn Panhypopituitarism

Wurm Michael , van der Werf-Grohmann Natascha , Krause Alexandra , Roemer-Pergher Cordula , Schwab Karl Otfried

Introduction: Standard dose for GH deficient children is 0.025 mg/kg per day given subcutaneously once daily. Inborn panhypopituitarism is a special subset of GH deficiency. Its management is difficult because several hormones need to be replaced. We present three patients with perinatal onset panhypopituitarism.Case reports: Case 1 is a 7-year-old boy who had hypoglycaemic seizure with reanimation due to circulatory arrest shortly after birth. Panhypopi...

hrp0084fc2.1 | Bone & Mineral Metabolism | ESPE2015

Whole Exome Sequencing Analysis of Patients with Autosomal Recessive Hypophophatemic Rickets Identified Mutations in DMP1, ENPP1 and SLC34A3

Li Dong , Tenenbaum-Rakover Yardena , Tian Lifeng , Hou Cuiping , Kim Cecilia , Hakonarson Hakon , Levine Michael

Background: Hypophosphatemic rickets (HR) is most commonly X-linked or autosomal dominant, but autosomal recessive (AR) forms have been described. ARHR1 (DMP1) and ARHR2 (ENPP1) share identical biochemical characteristics of excessive renal phosphate wasting due to increased circulating levels of the phosphatonin FGF23 and low serum levels of 1,25(OH)2D. By contrast, in hereditary hypophosphatemic rickets with hypercalciuria (HHRH) phosphaturia is ...

hrp0084fc2.2 | Bone & Mineral Metabolism | ESPE2015

Identification of Mutations in TBX1 and AIRE in Isolated Hypoparathyroidism Patients

Li Dong , Schnellbacher Sarah , Tian Lifeng , Hou Cuiping , Kim Cecilia , Hakonarson Hakon , Levine Michael

Background: Hypoparathyroidism may manifest either as an isolated disorder or as a component of a more complex syndrome. Molecular genetic studies indicate that mutations in PTH, CASR, GCM2 and GNA11 are causes of isolated hypoparathyroidism (IH) and mutations in GATA3, TBCE, FAM111A, AIRE and TBX1 are associated with different complex syndromes with hypoparathyroidism.Objec...

hrp0084fc2.4 | Bone & Mineral Metabolism | ESPE2015

Asfotase Alfa: Sustained Efficacy and Tolerability in Children with Hypophosphatasia Treated for 5 Years

Madson Katherine L , Rockman-Greenberg Cheryl , Moseley Scott , Odrljin Tatjana , Whyte Michael P

Background: Hypophosphatasia (HPP) is the rare inherited metabolic disorder resulting from loss-of-function mutation(s) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. TNSALP deficiency can cause a spectrum of complications in children including premature deciduous tooth loss, rickets, poor growth, and compromised physical function. We previously reported that children, 5–12 years old, with HPP and treated with asfotase alfa, a recombinant bone-targeted huma...