Pseudohypoparathyroidism
Pseudohypoparathyroidism is a rare genetic disorder characterized by the body's resistance to parathyroid hormone (PTH), leading to low blood calcium levels and high blood phosphate levels despite normal PTH production. This condition can manifest in several forms, notably Types 1A and 1B. Type 1A, also known as Albright's hereditary osteodystrophy, is marked by symptoms such as short stature, round facial features, and bone abnormalities, while Type 1B primarily affects the kidneys. The underlying cause is often linked to mutations in the GNAS gene, which plays a crucial role in the signaling pathways for PTH. Symptoms of the disorder may include muscle spasms, tingling sensations, and, in severe cases, convulsions due to hypocalcemia. Diagnosis typically involves blood and urine tests to assess calcium and phosphate levels, along with genetic testing to confirm a family history of the disorder. Treatment often includes calcium and vitamin D supplements, dietary modifications, and emergency interventions for acute hypocalcemia. Individuals with this condition are at a higher risk for other endocrine disorders, making ongoing medical care essential for managing health outcomes.
Pseudohypoparathyroidism
ALSO KNOWN AS: Albright’s hereditary osteodystrophy; Types 1A and 1B pseudohypoparathyroidism
DEFINITION Pseudohypoparathyroidism denotes a group of inherited disorders characterized by deficiency in the end-organ response to parathyroid hormone (PTH) and in some instances because of abnormal PTH receptors. The term pseudohypoparathyroidism is used because there is evidence of clinical hypoparathyroidism but serum PTH levels are normal.
Risk Factors
A family history of pseudohypoparathyroidism is the primary risk factor for the disease.
Etiology and Genetics
Parathyroid glands assist in the control of calcium use and removal by the body by producing parathyroid hormone, or PTH. PTH helps control calcium, phosphorus, and vitamin D levels within the blood and bone. Individuals with pseudohypoparathyroidism produce the required amount of PTH, but the body is “resistant” to its effect. This causes low blood calcium levels and high blood phosphate levels. Pseudohypoparathyroidism is very rare and is caused by abnormal genes. Type 1A, also called Albright’s hereditary osteodystrophy, is an inherited autosomal dominant trait, and therefore only one parent could potentially pass the defective gene to cause the condition. The condition results in short stature, round face, abnormally developed metacarpal and metatarsal bones, and subcutaneous bone ossification. Type 1B is less understood than type 1A and involves resistance to PTH only in the kidneys. Type 2 is very similar to type 1 in its clinical features, but the events that take place in the kidneys are different.
Type 2 pseudohypoparathyroidism also involves low blood calcium and high blood phosphate levels, but persons with this form do not develop the physical characteristics seen in those with Type 1A. Studies report the GNAS gene encodes the alpha-subunit of the stimulatory G proteins. These proteins are important in intracellular signal transduction of peptide and receptors. Heterozygous inactivating maternally inherited mutations of GNAS lead to a in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type 1A. Such mutations include translation initiation mutations, substitutions, nonsense mutations, splice-site mutations, and small insertions or deletions. E. Fernandezrebollo and colleagues found the GNAS gene of a five-year-old boy with pseudohypoparathyroidism to have a of exon 2 and part of 1 of de novo origin. This report demonstrated the first evidence for an inversion at the GNAS gene responsible for pseudohypoparathyroidism type 1.
Symptoms
Symptoms of pseudohypoparathyroidism are related to low levels of calcium, known as hypocalcemia. Hypocalcemia causes increased irritability of nerves, leading to numbness and tingling of the hands, feet, and lips. Tetany, which is manifested clinically as muscular spasms first affecting the hands and feet, is another symptom of pseudohypoparathyroidism. Laryngeal spasms can occur, leading to obstruction of the respiratory system. Severe hypocalcemia can lead to generalized convulsions in children. Other complications of hypocalcemia associated with pseudohypoparathyroidism may include other endocrine problems, leading to lowered sexual drive and lowered sexual development, lowered energy levels, and increased weight. Individuals with Albright’s hereditary osteodystrophy may have symptoms of calcium deposits under the skin and the physical characteristics of a round face and short neck and short stature in children.
Screening and Diagnosis
Blood tests are evaluated to determine calcium, phosphorus, and PTH levels. Urine tests are also utilized to determine key endocrine levels. Genetic testing is utilized to determine positive family history of the abnormalities. Magnetic resonance imaging (MRI) creates a detailed picture of the brain and surrounding nerve tissues and is helpful in diagnosing decreased levels of calcium causing increased irritability of nerve tissue.
Treatment and Therapy
Calcium and vitamin D supplements are prescribed to maintain proper calcium levels. A low-phosphorus diet may be necessary if blood phosphate levels remain higher than normal. Emergency treatment with intravenous calcium is needed if an individual presents an acute hypocalcemia crisis such as tetany, laryngeal spasm, and convulsions. Patients with low calcium levels are at risk of osteoporosis.
Prevention and Outcomes
Low blood calcium in pseudohypoparathyroidism is usually milder than in other forms of hypoparathyroidism. Proper medical attention and follow-up are important in prevention and treatment of other endocrine problems, as patients with type 1A pseudohypoparathyroidism have an increased occurrence of other endocrine abnormalities to include hypothyroidism and hypogonadism.
Bibliography
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