Pseudopseudohypoparathyroidism (Pseudo-PHP)

Hypoparathyroidism is a rare medical condition in which the body cannot produce enough parathyroid hormone (PTH) from the parathyroid glands.

PTH regulates the amount of phosphate and calcium in the blood by controlling how the body absorbs calcium during digestion and bone tissue breakdown. Without PTH, or when the body cannot respond to PTH, blood levels of calcium become very low, and phosphate levels increase.

People with pseudohypoparathyroidism (PHP) produce normal amounts of PTH, but they lack the receptors that respond to PTH.

Pseudohypoparathyroidism (pseudo-PHP, also called Albright hereditary osteodystrophy) is a rare heritable disease that has symptoms very similar to PHP. These include short stature, obesity, unusually short fingers and toes, as well as skeletal abnormalities, among other symptoms.

What causes pseudo-PHP?

Mutations in a gene called GNAS, which provides the instructions necessary to make a portion of the receptor that recognizes PTH signals, cause pseudo-PHP. However, it is not clear why some mutations may cause PHP and some cause pseudo-PHP. Researchers think that the difference between the two conditions is parental imprinting — the labeling of genes and chromosomes from each parent that regulates how the gene functions.

Is pseudo-PHP a heritable disease?

Pseudo-PHP can be inherited, though some cases may occur because of  spontaneous mutations.

Patients inherit pseudo-PHP in a dominant manner. This means they develop the disease even if they inherit a single copy of a disease-causing mutation. However, patients inherit pseudo-PHP only from their fathers. If they inherit the gene mutation from their mothers, they develop PHP.

How do doctors diagnose it?

Doctors can diagnose pseudo-PHP with blood tests to measure the levels of calcium, phosphorous, and PTH to exclude other forms of PHP.

X-ray imaging can detect bone abnormalities. Doctors usually confirm the diagnosis with genetic testing, looking for mutations in the GNAS gene.

How do doctors treat it?

There is no specific treatment for pseudo-PHP, but there are ways to manage the condition as well as the related disorders.