Pseudohypoparathyroidism is a genetic disorder in which the body is unable to respond to parathyroid hormone. Parathyroid hormone helps control calcium, phosphorous, and vitamin D levels in the bones and blood. Hypoparathyroidism is a similar condition in which the body does not make enough parathyroid hormone instead of not being able to respond to it (as in pseudohypoparathyroidism).
There are two different types of pseudohypoparathyroidism, both of which are caused by spelling mistakes (mutations) in certain genes. Type 1 can be further divided into three sub-types
Pseudohypoparathyroidism type 1A is a type of pseudohypoparathyroidism. Pseudohypoparathyroidism is when your body is unable to respond to parathyroid hormone, which is a hormone that controls the levels of calcium, phosphorous, and vitamin D in the blood. The symptoms are very similar to hypoparathyroidism (when parathyroid hormone levels are too low). The main symptoms are low calcium levels and high phosphate levels in the blood. This results in cataracts, dental problems, seizures, numbness, and tetany (muscle twitches and hand and foot spasms). Symptoms are generally first seen in childhood. People with this disorder are also resistant to other hormones, such as thyroid-stimulating hormone and gonadotropins. Type 1A is also associated with a group of symptoms referred to as Albright's hereditary osteodystrophy, which includes short stature, a round face, obesity, and short hand bones. Pseudohypoparathyroidism type 1A is caused by a spelling mistake (mutation) in the GNASgene and is inherited in an autosomal dominant manner.
Pseudohypoparathyroidism type 1B (PHP1B) is a genetic disorder that is caused by a lack of response (resistance) to parathyroid hormone (PTH) and other hormones such as thyroid-stimulating hormone (TSH). This condition is very similar to hypoparathyroidism (in which not enough PTH is produced), causing low calcium levels and high phosphate levels in the blood. Resistance to PTH in individuals with type 1B may be limited to the kidneys. The severity of the condition can vary considerably among affected individuals, even within the same family. Most individuals do not have an abnormal physical appearance and usually do not exhibit other endocrine abnormalities. In some cases, PHP1B is inherited in an autosomal dominant manner and is caused by mutations in either the GNAS or STX16 genes. In other cases, it has been shown to be sporadic (not inherited), caused byimprinting defects in the GNAS gene. The goals of treatment are to correct the calcium deficiency and prevent complications.
Pseudohypoparathyroidism type 1C is a genetic disorder that is very similar to hypoparathyroidism (parathyroid hormone levels are too low). However, pseudohypoparathyroidism is caused by no response to parathyroid hormone rather than having too little of the hormone itself. This causes low calcium and high phosphate levels in the blood. This condition is also associated with a group of symptoms referred to as Albright's hereditary osteodystrophy, which includes short stature, a round face, obesity, and short hand bones. This disorder is different than pseudohypoparathyroidism type 1A because people with type 1C do not have abnormal activity of a particular protein (stimulatory protein G (Gs alpha)). Type 1C is inherited in an autosomal dominant fashion and is caused by a specific spelling mistake (mutation) in the GNAS gene.
Pseudohypoparathyroidism type 2 lacks the physical appearance of type 1a.Since the genetic defect in type 2 is further down the signalling pathway than in type 1, there is a normal cAMP response to PTH stimulation despite the inherent abnormality in calcium regulation.
Pseudohypoparathyroidism is characterized by short stature, a round face, short neck, and shortened bones in the hands and feet. Intelligence usually ranges from low normal to mentally retarded. Headaches, weakness, tiring easily, lethargy, cataracts (clouding of the lens of the eye) and blurred vision or hypersensitivity to light may also be present. During childhood, seizures may occur. Teeth with underdeveloped enamel tend to erupt later than normal during infancy. Levels of calcium in the blood are usually low, while phosphate and the parathyroid hormone are elevated. Patients with Pseudohypoparathyroidism can lead a normal life.
Pseudohypoparathyroidism is a hereditary disorder inherited either through X- linked dominant genes or through autosomal dominant genes.
Human traits including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In X-linked dominant disorders, the female with only one X chromosome affected will develop the disease. However, the affected male always has a more severe condition. Sometimes, affected males die before birth so that only female patients survive.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
A defect in the the guanine nucleotide-binding protein may be responsible for some forms of Pseudohypoparathyroidism.
The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition.
Hypocalcemia in pseudohypoparathyroidism is usually milder than in other forms of hypoparathyroidism.
Treatment consists of calcium and vitamin D supplements, to maintain high calcium levels without the help of PTH. If serum phosphate stays high, a low-phosphorus diet or phosphate binders (such as calcium carbonate, calcium acetate, or sevelamer HCl) may be necessary.
Alternative Names : Albright's hereditary osteodystrophy; Types 1A and 1B pseudohypoparathyroidism