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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
Parathyroid hormone resistance syndromes - Inactivating PTH/PTHrP signaling disorders (iPPSDs).
Metabolic disorders caused by impairments of the Gsα/cAMP/PKA pathway affecting the signaling of PTH/PTHrP lead to features caused by non-responsiveness of target organs, in turn leading to manifestations similar to the deficiency of the hormone itself. Pseudohypoparathyroidism (PHP) and related disorders derive from a defect of the α subunit of the stimulatory G protein (Gsα) or of downstream effectors of the same pathway, such as the PKA regulatory subunit 1A and the phosphodiesterase type 4D. The increasing knowledge on these diseases made the actual classification of PHP outdated as it does not include related conditions such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), so that a new nomenclature and classification has been recently proposed grouping these disorders under the term "inactivating PTH/PTHrP signaling disorder" (iPPSD). This review will focus on the pathophysiology, clinical and molecular aspects of these rare, heterogeneous but closely related diseases.
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