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Disease Profile

Albright’s hereditary osteodystrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

AHO; Albright hereditary osteodystrophy; Pseudohypoparathyroidism with Albright hereditary osteodystrophy

Categories

Congenital and Genetic Diseases

Summary

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).[1][2] 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).[2] This condition is inherited in anautosomal dominant manner due to a mutation in the GNAS gene.[1] 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.[3]

Symptoms

Albright's hereditary osteodystophy is a genetic disorder that can cause many different symptoms. People with this disorder usually have short stature, obesity, round face, short bones in the hands and feet (brachydactyly), subcutaneous (under the skin) ossifications (replacement of cartilage by bone), and dimples on affected knuckles.[1][3][2] Some people may have mild developmental delay.[1]

People with this disorder usually are resistant to parathyroid hormone (which is a condition called pseudohypoparathyroidism). This causes low levels of calcium in the bones and the blood. Low levels of calcium in the blood (hypocalcemia) can cause numbness, seizures, cataracts (cloudy lens in the eye), dental issues, and tetany (muscle twitches and hand and foot spasms).[3][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal calcium-phosphate regulating hormone level
0100530
Gynecomastia
Enlarged male breast
0000771
Hyperphosphatemia
High blood phosphate levels
0002905
Hyperthyroidism
Overactive thyroid
0000836
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Multiple cafe-au-lait spots
0007565
Obesity
Having too much body fat
0001513
Precocious puberty
Early onset of puberty
Early puberty

[ more ]

0000826
Round face
Circular face
Round facial appearance
Round facial shape

[ more ]

0000311
Skeletal dysplasia
0002652
30%-79% of people have these symptoms
Abnormality of the penis
0000036
Coarse facial features
Coarse facial appearance
0000280
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Dry skin
0000958
Goiter
Enlarged thyroid gland in neck
0000853
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Irregular menstruation
Menstrual irregularity
0000858
Scoliosis
0002650
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin

[ more ]

0001482
Thin skin
0000963
5%-29% of people have these symptoms
Abnormality of the hip bone
Abnormality of the hips
0003272
Alopecia
Hair loss
0001596
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Neoplasm of the breast
Breast tumor
Tumours of the breast

[ more ]

0100013
Neoplasm of the thyroid gland
0100031
Polycystic ovaries
0000147
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Sarcoma
Cancer of connective tissue
Malignant connective tissue tumor

[ more ]

0100242
Testicular neoplasm
Testicular tumor
0010788
Thickened calvaria
Increased thickness of skull cap
Thickened skull cap

[ more ]

0002684
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

Cause

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.[1]

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)).[1][2]

Treatment

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.[3]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Albright's hereditary osteodystrophy. Click on the link to view a sample search on this topic.

        References

        1. Kottler ML, Linglart A, Carel JC. Albright hereditary osteodystrophy. Orphanet encyclopedia. January 2004; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=665. Accessed 10/17/2012.
        2. GNAS. Genetics Home Reference (GHR). January 2009; https://ghr.nlm.nih.gov/gene/GNAS. Accessed 10/17/2012.
        3. Topiwala S. Pseudohypoparathyroidism. MedlinePlus. July 2012; https://www.nlm.nih.gov/medlineplus/ency/article/000364.htm. Accessed 10/17/2012.

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