Albright's hereditary osteodystrophy

Albright's hereditary osteodystophy (AHO) is caused by spelling mistakes (mutations) in the GNAS gene. This gene is responsible for creating a subunit of a certain protein called a G protein. The G protein helps regulate the activity and production of certain hormones. It is also involved in regulating the development of bone and helps prevent the body from producing bone tissue in the wrong place. Thus, a mutation in the GNAS gene leads to abnormal creation of the G protein, which then leads to issues with the activity of certain hormones in the body and abnormal bone growth.

The hormone resistance that can be associated with AHO, in particular the resistance to parathyroid hormone (PTH), depends on whether the mutation is inherited from the mother or the father. This is due to a concept called genomic imprinting. Everyone has two copies of each gene in their body, one from their mother and one from their father. Usually both copies of the gene are active or "turned on." Although, some genes are only active when inherited from a person's mother while other genes are only active when inherited from a person's father. When the disorder is inherited from the mother, in addition to AHO there are also symptoms associated with the resistance to certain hormones (pseudohypoparathyroidism type 1a (PHP1a)). If inherited from the father, there are no hormone issues associated with the AHO (pseudopseudohypoparathyroidism (PPHP)).

This condition is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. There is nothing that either parent can do, before or during a pregnancy, to cause a child to have this condition. In some cases, an affected person inherits the mutation from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or 'turned on,' in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's mother (the maternal copy) is active, while for other genes, only the copy inherited from a person's father (the paternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting. Hormone resistance and, in particular resistance to parathyroid hormone (PTH), only occurs when the gene mutation is inherited from the mother (a condition called pseudohypoparathyroidism type 1a (PHP1a)).

When a mutation that causes AHO is inherited from a person's mother, the affected individual will usually have AHO accompanied by a resistance to multiple hormones (a condition called pseudohypoparathyroidism type 1A, or PHP1A). Thus, a woman with AHO has a 50% chance in each pregnancy of having a child with PHP1A and AHO.

A paternally-inherited mutation can result in AHO without endocrine problems; this form of the condition is also called pseudopseudohypoparathyroidism (PPHP). Thus, a man with AHO has a 50% chance in each pregnancy of having a child with AHO without hormone resistance (pseudopseudohypoparathyroidism).

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).

The symptoms of these two conditions are similar and are caused by low calcium levels and high phosphate levels in the blood. This may cause cataracts (clouding of the lens of the eye), dental problems, numbness, seizures, or tetany (muscle twitches and hand and foot spasms). These symptoms are usually first seen in childhood.

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. Click on the links below for more information on the various types of pseudohypoparathyroidism.

Pseudohypoparathyroidism type 1A
Pseudohypoparathyroidism type 1B
Pseudohypoparathyroidism type 1C
Pseudohypoparathyroidism type 2

Albright's hereditary osteodystrophy (AHO) is a rare disorder with a wide range of signs and symptoms, including short stature, obesity, round face, subcutaneous ossifications (formation of bone under the skin), and short fingers and toes (brachydactyly). When the disorder is inherited from the mother, the features of AHO can be associated with resistance to certain hormones, in particular the parathyroid hormone (PTH). This is called pseudohypoparathyroidism type 1a (PHP1a). When inherited from the father, an individual will have AHO without any hormone issues, which is called pseudopseudohypoparathyroidism (PPHP). This condition is inherited in anautosomal dominant manner due to a mutation in the GNAS gene. Treatment consists of calcium and vitamin D supplements. If there are high levels of phosphate in the blood, it may be recommended to eat a low-phosphorous diet or take medications called phosphate binders to help lower the levels of phosphate.

Treatment with calcium and vitamin D supplements help maintain normal levels of calcium in the blood. If there are high levels of phosphate in the blood, it may be recommended to eat a low-phosphorous diet or take medications called phosphate binders to help lower the levels of phosphate. Examples of phosphate binders include calcium carbonate, calcium acetate, and sevelamer HCl.