Summary about Disease
Albright Hereditary Osteodystrophy (AHO) is a rare genetic disorder primarily characterized by resistance to parathyroid hormone (PTH). This resistance leads to hypocalcemia (low blood calcium), hyperphosphatemia (high blood phosphorus), and elevated PTH levels. AHO also presents with distinctive physical features including short stature, round face, brachydactyly (shortening of fingers and toes), and subcutaneous ossifications (bone formation under the skin).
Symptoms
Skeletal: Short stature, shortened fingers and toes (brachydactyly, particularly of the 4th and 5th metacarpals/metatarsals), progressive bone formation in the skin and other tissues (osteoma cutis).
Endocrine: Hypocalcemia (can lead to muscle cramps, tetany, seizures), hyperphosphatemia.
Facial: Round face.
Other: Cognitive impairment (in some cases), dental problems.
Causes
AHO is caused by mutations in the GNAS gene located on chromosome 20q13.3. This gene encodes the alpha subunit of the stimulatory G protein (GsĪ±), which is crucial for the proper signaling of several hormones, including PTH. The inheritance pattern can vary. When inherited from the mother, it typically results in AHO with hormone resistance (Pseudohypoparathyroidism type 1A). When inherited from the father, it usually results in only the physical features of AHO (Pseudo-pseudohypoparathyroidism). Genetic imprinting (parent-of-origin effect) plays a significant role in the presentation of the disease.
Medicine Used
Calcium Supplements: To correct hypocalcemia.
Vitamin D Analogs (e.g., Calcitriol): To improve calcium absorption and help regulate calcium and phosphate levels.
Phosphate Binders: To reduce elevated phosphate levels. These are often used with meals.
In some cases, PTH injections are used to overcome resistance.
Is Communicable
No. AHO is a genetic disorder and is not communicable or contagious. It cannot be spread from person to person.
Precautions
Genetic Counseling: For families with a history of AHO to understand the risk of inheritance.
Regular Monitoring: Of calcium, phosphorus, and PTH levels, especially in children, to adjust medication dosages as needed.
Fall Prevention: Due to potential muscle weakness or seizures secondary to hypocalcemia.
Dental Care: Due to the potential for dental abnormalities.
How long does an outbreak last?
AHO is not an "outbreak" situation. It's a chronic, genetic condition. The symptoms are persistent throughout the individual's life, although the severity and manifestation of symptoms can vary over time. There is no "cure," and management focuses on controlling the symptoms and preventing complications.
How is it diagnosed?
Clinical Evaluation: Assessment of physical features (short stature, round face, brachydactyly).
Laboratory Tests: Blood tests to measure calcium, phosphorus, PTH, and alkaline phosphatase levels.
Radiographic Studies: X-rays to evaluate skeletal abnormalities (e.g., shortened metacarpals/metatarsals, subcutaneous ossifications).
Genetic Testing: To identify mutations in the GNAS gene, confirming the diagnosis and aiding in genetic counseling.
Endocrine Testing: Infusion of PTH can show resistance, indicating Pseudohypoparathyroidism.
Timeline of Symptoms
Infancy/Early Childhood: Symptoms such as round face and potentially subtle skeletal abnormalities may be noticeable. Hypocalcemia may present with seizures.
Childhood/Adolescence: Short stature becomes more apparent. Brachydactyly and subcutaneous ossifications may develop. Dental abnormalities might be identified. Endocrine abnormalities will be noticed during routine blood screenings if the patient has not been previously diagnosed.
Adulthood: Management of chronic symptoms, including hypocalcemia, hyperphosphatemia, and skeletal issues. Monitoring for complications.
Important Considerations
Variable Expressivity: The severity and specific features of AHO can vary considerably among affected individuals, even within the same family.
Parent-of-Origin Effect: The inheritance of the GNAS mutation from the mother versus the father can significantly impact the presentation of the disease.
Multidisciplinary Care: Management often requires a team of specialists, including endocrinologists, geneticists, orthopedic surgeons, and dentists.
Quality of Life: Focus on managing symptoms to improve the individual's quality of life and functional abilities.