Pseudohypoparathyroidism, acrodysostosis, progressive osseous heteroplasia: different names for the same spectrum of dis
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MINI REVIEW
Pseudohypoparathyroidism, acrodysostosis, progressive osseous heteroplasia: different names for the same spectrum of diseases? Francesca Marta Elli1 Giovanna Mantovani ●
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Received: 9 June 2020 / Accepted: 24 October 2020 © The Author(s) 2020
Abstract Pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, derives from a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key component of the PTH/PTHrP signaling pathway. Since its first description, different studies unveiled, beside the molecular basis for PHP, the existence of different subtypes and of diseases in differential diagnosis associated with genetic alterations in other genes of the PTH/PTHrP pathway. The clinical and molecular overlap among PHP subtypes and with different but related disorders make both differential diagnosis and genetic counseling challenging. Recently, a proposal to group all these conditions under the novel term “inactivating PTH/PTHrP signaling disorders (iPPSD)” was promoted and, soon afterwards, the first international consensus statement on the diagnosis and management of these disorders has been published. This review will focus on the major and minor features characterizing PHP/iPPSDs as a group and on the specificities as well as the overlap associated with the most frequent subtypes.
Introduction In 1942, Fuller Albright described pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, and not many years passed since he realized the complexity of the disease and recognized the existence of different subtypes. In addition to the best known PHP type 1A (PHP1A) patients, characterized by increased PTH serum levels, hypocalcemia and hyperphosphatemia and a constellation of clinical abnormalities collectively named as Albright Hereditary Osteodystrophy (AHO) (brachydactyly, overweight/obesity, pre and/or postnatal growth retardation, dysmorphic facies with a rounded face, ectopic subcutaneous ossifications, cognitive and/behavioral defects and additional hormone resistances), other patients displayed the presence of physical features of AHO without resistance to the action of PTH and the condition was termed
* Giovanna Mantovani [email protected] 1
Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
pseudopseudohypoparathyroidism (PPHP) [1–8], while others showed isolated PTH resistance with apparently no other clinical manifestations (PHP type 1B, PHP1B) [9]. The exact prevalence of PHP is unknown. Studies published in 2000 and 2016 estimated the prevalence to be 0.34 in 100,000 in Japan, 1.1 in 100,000 in Denmark and 0.66 in 100.000 in Italy ([10], Orphanet). The investigation of the pathogenetic mechanism confirmed that the metabolic defect underlying the disease was the lack of responsiveness to the action of PTH in target tissues due to a defective activity o
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