What are the symptoms? AHO with pseudohypoparathyroidism (PHP) In addition to AHO, in PHP the body is unable to respond to various hormones. One such hormone is parathyroid hormone (PTH), which maintains levels of calcium and phosphate in the blood. In PHP, parathyroid hormone is produced in normal or increased amounts by the parathyroid glands and released into the blood. However, the body is resistant to its effects causing hypocalcaemia (low calcium levels), and hyperphosphatemia (high phosphate levels). Signs of hypocalcaemia include tingling in the fingers, muscle cramps, possible seizures (fits) and, in the longer term, cataracts. Hypocalcaemia typically begins in mid-childhood. Individuals with PHP are often resistant to thyroid stimulating hormone (TSH), which makes the thyroid gland produce thyroid hormone. The effects of lack of thyroid hormone are a tendency to gain weight easily and to feel the cold, dry skin and hair, and a lack of energy. Pseudo-pseudohypoparathyroidism (PPHP) People with this condition have the physical characteristics of AHO but they do not have any hormone abnormalities (that is, they just have AHO). The complicated name arose for historical reasons. What are the causes? Mutations in a gene called GNAS1 carried on chromosome 20 cause these conditions. Pseudohypoparathyroidism can also occur on its own without AHO and is caused by a different type of genetic change affecting the same GNAS1 gene. How is it diagnosed? The physical features of AHO are diagnosed by examination usually by an experienced clinical geneticist or endocrinologist. It may be necessary to do X-rays particularly of the hands, feet and spine to confirm the diagnosis. Many of the features of AHO are not specific to this condition, that is, they can have many different causes of which genetic changes in the GNAS1 gene are only one. Chromosome testing may be requested to look for some other conditions that can resemble AHO. PHP is diagnosed by testing of the blood and urine for biochemical changes associated with resistance to PTH and TSH, such as low calcium, raised phosphate, high PTH, low thyroxine and high TSH levels. In people in whom the diagnosis is strongly suspected, specific testing for genetic changes (mutations) in the GNAS1 gene is available, which picks up an abnormality in about 70 per cent of affected people. How is it treated? Fortunately, the low calcium levels experienced with this condition can be treated with vitamin D, and low thyroid levels can be treated with thyroxine. Inheritance patterns and prenatal diagnosis Inheritance patternsAHO is inherited as an autosomal dominant trait but the presence or absence of PHP depends on the parent of origin. We each have two copies of the GNAS1 gene, one from each parent. People with AHO have a mutation (genetic change) in one GNAS1 gene copy. If the copy with the mutation is the one they inherited from their mother, they usually have associated PHP. If it is the one they inherited from their father then they do not usually have any hormone abnormalities (that is, they have PPHP). A person with AHO has a 50 per cent chance in each pregnancy that their baby will inherit the GNAS1 mutation, regardless of the sex of the baby. However, many individuals with AHO have unaffected parents because the mutation has arisen sporadically. Prenatal diagnosisAHO can be tested for using chorionic villus sampling or amniocentesis during pregnancy, but only if the specific genetic change causing AHO in the family has been identified. Genetic counselling is strongly recommended for individuals and families affected by this condition. Is there support? There is no support group for Albright hereditary osteodystrophy in the UK. Cross referrals to other entries in The Contact a Family Directory are intended to provide relevant support for those particular features of the disorder. Organisations identified in those entries do not provide support specifically for Albright hereditary osteodystrophy. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families.
What are the symptoms? AHO with pseudohypoparathyroidism (PHP) In addition to AHO, in PHP the body is unable to respond to various hormones. One such hormone is parathyroid hormone (PTH), which maintains levels of calcium and phosphate in the blood. In PHP, parathyroid hormone is produced in normal or increased amounts by the parathyroid glands and released into the blood. However, the body is resistant to its effects causing hypocalcaemia (low calcium levels), and hyperphosphatemia (high phosphate levels). Signs of hypocalcaemia include tingling in the fingers, muscle cramps, possible seizures (fits) and, in the longer term, cataracts. Hypocalcaemia typically begins in mid-childhood. Individuals with PHP are often resistant to thyroid stimulating hormone (TSH), which makes the thyroid gland produce thyroid hormone. The effects of lack of thyroid hormone are a tendency to gain weight easily and to feel the cold, dry skin and hair, and a lack of energy. Pseudo-pseudohypoparathyroidism (PPHP) People with this condition have the physical characteristics of AHO but they do not have any hormone abnormalities (that is, they just have AHO). The complicated name arose for historical reasons.
What are the causes? Mutations in a gene called GNAS1 carried on chromosome 20 cause these conditions. Pseudohypoparathyroidism can also occur on its own without AHO and is caused by a different type of genetic change affecting the same GNAS1 gene.
How is it diagnosed? The physical features of AHO are diagnosed by examination usually by an experienced clinical geneticist or endocrinologist. It may be necessary to do X-rays particularly of the hands, feet and spine to confirm the diagnosis. Many of the features of AHO are not specific to this condition, that is, they can have many different causes of which genetic changes in the GNAS1 gene are only one. Chromosome testing may be requested to look for some other conditions that can resemble AHO. PHP is diagnosed by testing of the blood and urine for biochemical changes associated with resistance to PTH and TSH, such as low calcium, raised phosphate, high PTH, low thyroxine and high TSH levels. In people in whom the diagnosis is strongly suspected, specific testing for genetic changes (mutations) in the GNAS1 gene is available, which picks up an abnormality in about 70 per cent of affected people.
How is it treated? Fortunately, the low calcium levels experienced with this condition can be treated with vitamin D, and low thyroid levels can be treated with thyroxine.
Inheritance patterns and prenatal diagnosis Inheritance patternsAHO is inherited as an autosomal dominant trait but the presence or absence of PHP depends on the parent of origin. We each have two copies of the GNAS1 gene, one from each parent. People with AHO have a mutation (genetic change) in one GNAS1 gene copy. If the copy with the mutation is the one they inherited from their mother, they usually have associated PHP. If it is the one they inherited from their father then they do not usually have any hormone abnormalities (that is, they have PPHP). A person with AHO has a 50 per cent chance in each pregnancy that their baby will inherit the GNAS1 mutation, regardless of the sex of the baby. However, many individuals with AHO have unaffected parents because the mutation has arisen sporadically. Prenatal diagnosisAHO can be tested for using chorionic villus sampling or amniocentesis during pregnancy, but only if the specific genetic change causing AHO in the family has been identified. Genetic counselling is strongly recommended for individuals and families affected by this condition.
Is there support? There is no support group for Albright hereditary osteodystrophy in the UK. Cross referrals to other entries in The Contact a Family Directory are intended to provide relevant support for those particular features of the disorder. Organisations identified in those entries do not provide support specifically for Albright hereditary osteodystrophy. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families.