Clin Osteol 2005; 10(1): 3-6

Pseudohypoparathyroidism in childhoodArticles

M. Bayer

Pseudohypoparathyroidism (PHP) is characterised by biochemical hypoparathyroidism with elevated parathyroid hormone (PTH) levels and reduced target tissue responsiveness to PTH. Patients with PHP type 1a show a group of developmental defects termed Albright hereditary osteodystrophy (AHO) and exhibit resistance to additional hormones because of heterozygous, inactivating mutation in GNAS1, the gene for the alpha-subunit of the Gs-protein, which disrupts Gs-protein-coupled signal transduction pathways. Within PHP type 1a families some individuals show AHO but have normal hormone responsiveness, a variant phenotype termed pseudo-pseudohypoparathyroidism (PPHP).By contrast, patients with PHP type 1b ma­ nifest only PTH resistance and lack features of AHO. Although an epigenetic defect in GNAS1 has been identified in subjects with PHP1b, the gene­ tic defect is unknown. Patiens with PHP type Ic show both AHO and resistance to multiple hormones with normal Gs-protein activity. Rare PHP type II has no confirmed genetic or familial basis. Patients present additional hormones resistance, normal Gs-protein, and lack AHO phenotype. Treatment of PHP with vitamin D derivatives alleviates symptoms of hypocalcemia and may prevent bone demineral rience with several PHP children.

Keywords: pseudohypoparathyroidism, pseudopseudohypoparathyroidism, Gs-alpha protein, childhood.

Published: June 11, 2005  Show citation