Pseudohypoparathyroidism (PHP) is a rare genetic disorder characterized by end-organ resistance to the parathyroid hormone (PTH) and hypocalcemia. It is a heterogeneous disorder, with four distinct clinical phenotypes: PHP type 1a (PHP1a), PHP type 1b (PHP1b), PHP type 2a (PHP2a), and PHP type 2b (PHP2b). PHP1a is the most severe form and is caused by mutations in the GNAS gene located on chromosome 20. PHP1b is caused by mutations in the Gsα subunit of the stimulatory G protein, while PHP2a is caused by mutations in the Gαi subunit of the inhibitory G protein. PHP2b is caused by mutations in the Gαq subunit of the stimulatory G protein.
The main clinical features of PHP include short stature, brachydactyly, round face, low serum calcium levels, low PTH levels, and resistance to the action of PTH. Additional physical findings may include abnormal tooth formation, facial dysmorphism, and premature closure of the epiphyses. PHP is diagnosed based on clinical features, laboratory tests, and genetic testing. Treatment generally consists of oral calcium and vitamin D supplementation and, in some cases, hormone replacement therapy.
PHP is an important disorder to recognize, as it can cause significant morbidity if left untreated. Early diagnosis and treatment is essential for proper management of the condition.
References
Bhaskar, S., & Pollak, M. (2014). Pseudohypoparathyroidism: Mechanism, diagnosis, and treatment. Indian Journal of Endocrinology and Metabolism, 18(1), 5-10. https://doi.org/10.4103/2230-8210.122045
Kumar, S., & Gopalakrishnan, G. (2016). Pseudohypoparathyroidism: A review. Indian Journal of Endocrinology and Metabolism, 20(1), 1–7. https://doi.org/10.4103/2230-8210.173952
Mastorakos, G., & Kaltsas, G. (2015). Molecular and genetic aspects of pseudohypoparathyroidism. Frontiers in Endocrinology, 6(64), 1-10. https://doi.org/10.3389/fendo.2015.00064