ESPE Abstracts (2016) 86 FC2.2

aDivision of Experimental Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lübeck, Luebeck, Germany; bFondazione IRCCS Ca’ Granda Ospedal Maggiore Policlinico, Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; cAPHM, Hôpital la Conception, Laboratory of Molecular Biology, Marseille, France; dDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium; eMolecular (Epi)Genetics Laboratory, BioAraba National Health Institute, Hospital Universitario Araba-Txagorritxu, Vitoria-Gasteiz, Spain; fAPHP, Reference center for rare disorders of the mineral metabolism and Plateforme d’Expertise Maladies Rares Paris-Sud, Le Kremlin Bicêtre, 94270, Paris, France; gINSERM U1169, Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Paris, France; hDepartment of Endocrinology and Nutrition, La Paz University Hospital, Madrid, Spain; iDepartment of Public Health and Pediatric Sciences, University of Torino, Torino, Italy; jService de Biochimie et Génétique Moléculaires, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France; kDepartment of Pediatrics, Division of Endocrinology and Diabetes, Marmara University, Istanbul, Turkey; lDepartment of Endocrinology and Diabetes, Birmingham Children’s Hospital, Birmingham, UK

Background: Disorders related to an impairment in parathyroid hormone (PTH) signaling pathway are historically classified under the term pseudohypoparathyroidism (PHP), that now encompasses rare, related but highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and an in vitro assay of Gsα protein activity. However, this classification does not take into consideration other related diseases like acrodysostosis (ACRDYS) or Progressive Osseous Heteroplasia (POH), as well as recent associations to phenotypes and genetic/epigenetic background of the different subtypes.

Objective and hypotheses: The EuroPHP network met on three different occasions with the major goal of developing a new classification that encompasses all disorders with an impairment in PTH and/or PTHrP cAMP-mediated pathway.

Method: An extensive review of the literature was performed. Several meetings were organized to discuss about a new, more effective and accurate way to describe disorders related to abnormalities of the PTH signaling pathway. This led to the realization of a novel terminology and classification of these disorders.

Results: After a selection of major and minor criteria to consider for the diagnosis of these disorders, we proposed to group them under the term of “inactivating PTH/PTHrP signaling disorders”, abbreviated as iPPSD. This terminology: i) defines the common mechanism responsible for all diseases, ii) does not require a confirmed genetic defect, iii) avoids ambiguous terms like “pseudo”, iiii) eliminates the clinical or molecular overlap between diseases.

Conclusion: We believe that the use of this nomenclature and classification will facilitate the development of rationale and comprehensive international guidelines for the diagnosis and treatment of iPPSDs.

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