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Loss of Functional Osteoprotegerin: More Than a Skeletal Problem.
Grasemann, Corinna; Unger, Nicole; Hövel, Matthias; Arweiler-Harbeck, Diana; Herrmann, Ralf; Schündeln, Michael M; Müller, Oliver; Schweiger, Bernd; Lausch, Ekkehart; Meissner, Thomas; Kiewert, Cordula; Hauffa, Berthold P; Shaw, Nick J.
Afiliación
  • Grasemann C; Pediatric Endocrinology and Diabetology, Klinik für Kinderheilkunde II and.
  • Unger N; Center for Rare Bone Diseases, EZSE and Departments of.
  • Hövel M; Center for Rare Bone Diseases, EZSE and Departments of.
  • Arweiler-Harbeck D; Endocrinology, Diabetology, and Metabolism.
  • Herrmann R; Center for Rare Bone Diseases, EZSE and Departments of.
  • Schündeln MM; Orthopedics and Trauma Surgery.
  • Müller O; Center for Rare Bone Diseases, EZSE and Departments of.
  • Schweiger B; ENT, and.
  • Lausch E; Pediatric Neonatology, Klinik für Kinderheilkunde I and.
  • Meissner T; Pediatric Hematology and Oncology, Klinik für Kinderheilkunde III and Departments of.
  • Kiewert C; Neurosurgery.
  • Hauffa BP; Radiology and Neuroradiology, University Hospital Essen and The University of Duisburg-Essen, 45122 Essen, Germany.
  • Shaw NJ; Pediatric Genetics, Children's Hospital, University of Freiburg, 79106 Freiburg, Germany.
J Clin Endocrinol Metab ; 102(1): 210-219, 2017 01 01.
Article en En | MEDLINE | ID: mdl-27809640
Introduction: Juvenile Paget's disease (JPD), an ultra-rare, debilitating bone disease due to loss of functional osteoprotegerin (OPG), is caused by recessive mutations in TNFRFSF11B. A genotype-phenotype correlation spanning from mild to very severe forms is described. Aim: This study aimed to describe the complexity of the human phenotype of OPG deficiency in more detail and to investigate heterozygous mutation carriers for clinical signs of JPD. Patients: We investigated 3 children with JPD from families of Turkish, German, and Pakistani descent and 19 family members (14 heterozygous). Results: A new disease-causing 4 bp-duplication in exon 1 was detected in the German patient, and a microdeletion including TNFRFSF11B in the Pakistani patient. Skeletal abnormalities in all affected children included bowing deformities and fractures, contractures, short stature and skull involvement. Complex malformation of the inner ear and vestibular structures (2 patients) resulted in early deafness. Patients were found to be growth hormone deficient (2), displayed nephrocalcinosis (1), and gross motor (3) and mental (1) retardation. Heterozygous family members displayed low OPG levels (12), elevated bone turnover markers (7), and osteopenia (6). Short stature (1), visual impairment (2), and hearing impairment (1) were also present. Conclusion: Diminished OPG levels cause complex changes affecting multiple organ systems, including pituitary function, in children with JPD and may cause osteopenia in heterozygous family members. Diagnostic and therapeutic measures should aim to address the complex phenotype.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteítis Deformante / Osteoprotegerina / Mutación Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteítis Deformante / Osteoprotegerina / Mutación Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos