Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects.
Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects.
Pseudohypoparathyroidism (PHP), pseudo-PHP, acrodysostosis, and progressive osseous heteroplasia are heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, a stocky build, ectopic ossifications (features associated with Albright's hereditary osteodystrophy), as well as laboratory abnormalities consistent with hormone resistance, such as hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) and thyroid-stimulating hormone levels.
Short metacarpals and/or metatarsals are typically observed in pseudohypoparathyroidism (PHP) type Ia (PHP1A) or pseudo-PHP (PPHP), disorders caused by inactivating GNAS mutations involving exons encoding the alpha-subunit of the stimulatory G protein (Gsα).
Normalization of biochemical parameters after the procedure demonstrated that renal tubular resistance to PTH is sufficient to explain the calcium/phosphate abnormalities observed in PHP-1A.
Proximal renal tubular resistance to PTH and thus hypocalcemia and hyperphosphatemia, frequently in presence of brachydactyly, ectopic ossification, early-onset obesity, or short stature are common features of PHP.
Mutations in PRMT7 have been recently shown to be implicated in a phenotype with intellectual disability, short stature and brachydactyly, and considered to be a phenocopy of pseudohypoparathyroidism.
The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity.
Pseudohypoparathyroidism (PHP) and related disorders exemplify an unusual form of hormone resistance as the underlying molecular defect is a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key regulator of cAMP signaling pathway, or, as more recently described, of downstream effector proteins of the same pathway, such as PKA regulatory subunit 1A (R1A) and phosphodyestarase type 4D (PDE4D).
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone.
These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gsα mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described.