Pseudopseudohypoparathyroidism is a rare inherited disorder caused by mutations in the GNAS-1 gene, resulting in abnormal response to parathyroid hormone. Patients develop Albright hereditary osteodystrophy, but unlike pseudohypoparathyroidism, blood mineral levels are normal. The disease is labeled pseudoPHP because it shares some characteristics of PHP but does not affect blood mineral levels. The disease is caused by imprinting, and patients who receive a mutated gene from their mothers develop problems with blood mineral levels.
Pseudopseudohypoparathyroidism, also known as pseudoPHP or PPHP, is a rare inherited disorder caused by an abnormal response to parathyroid hormone. A variety of mutations in a gene located on the twentieth chromosome can provoke this disease. Patients with pseudoPHP typically develop Albright hereditary osteodystrophy (AHO), which causes abnormalities in bone structure and physical appearance. Unlike patients with pseudohypoparathyroidism (PHP), those with pseudoPHP have no abnormalities in blood levels of the minerals calcium and phosphorus.
Mutations in a gene called guanine nucleotide binding protein alpha-stimulating polypeptide 1 (GNAS-1) are responsible for causing pseudopseudohypoparathyroidism. Different families affected by the disease have shown different specific mutations within this gene. As a result of the altered deoxyribonucleic acid (DNA) sequence of GNAS-1, there is an abnormal cellular response to parathyroid hormone.
Patients with pseudopseudohypoparathyroidism typically develop a condition called AHO. These patients often have characteristic appearances, including round faces, short stature, and obesity. They commonly have abnormal deposits of calcification throughout their bodies, a process also known as heterotopic calcification. Additionally, patients with AHO may have bone deformities, including short fourth and fifth fingers, and curves in the bones of the arms. Occasionally patients with AHO have deficits in the senses of smell and taste.
PHP is the term used to describe diseases caused by other mutations in GNAS-1. Unlike patients with pseudoPHP, these patients have abnormalities in blood levels of calcium and phosphate. Some PHP patients also exhibit the characteristic physical findings of AHO.
Despite the fact that patients with pseudopseudohypoparathyroidism have an abnormal response to parathyroid hormone, they typically have normal blood calcium and phosphate levels. This was somewhat unexpected for the researchers who initially studied the disease, as parathyroid hormone plays a vital role in monitoring the levels of these minerals within the body. For this reason they labeled the disease as pseudoPHP because it shares some characteristics of PHP but does not affect the blood mineral levels of the body.
Whether a patient develops pseudoPHP or PHP may depend on which parent the individual inherited the mutated copy of GNAS-1. This genetic phenomenon is known as imprinting. Patients who receive a mutated gene from their mothers develop problems with their blood levels of calcium and phosphate because the maternal gene is turned on in the kidneys, organs that respond to parathyroid hormone and can alter blood mineral levels. In contrast, patients who receive a mutated gene from their fathers have no problems with blood mineral levels because the unaltered maternal copy of GNAS-1 is activated in the kidneys.
Protect your devices with Threat Protection by NordVPN
