Hypocalcemia, Autosomal Dominant 1 (HYPOC1)

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MedlinePlus Genetics: ⁴² Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same.

MalaCards based summary: Hypocalcemia, Autosomal Dominant 1, also known as autosomal dominant hypocalcemia, is related to hyperparathyroidism, neonatal severe and hypophosphatemic rickets, autosomal dominant, and has symptoms including seizures, muscle cramp and carpopedal spasm. An important gene associated with Hypocalcemia, Autosomal Dominant 1 is CASR (Calcium Sensing Receptor), and among its related pathways/superpathways are Signal Transduction and GPCR downstream signalling. The drugs Zoledronic acid and Magnesium sulfate have been mentioned in the context of this disorder. Affiliated tissues include kidney, eye and brain, and related phenotypes are emotional lability and depression

OMIM®: ⁵⁷ Autosomal dominant hypocalcemia-1 is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria with nephrocalcinosis or kidney stones; and more than 35% have ectopic and basal ganglia calcifications (summary by Nesbit et al., 2013). Thakker (2001) noted that patients with gain-of-function mutations in the CASR gene, resulting in generally asymptomatic hypocalcemia with hypercalciuria, have low-normal serum PTH concentrations and have often been diagnosed with hypoparathyroidism because of the insensitivity of earlier PTH assays. Because treatment with vitamin D to correct the hypocalcemia in these patients causes hypercalciuria, nephrocalcinosis, and renal impairment, these patients need to be distinguished from those with other forms of hypoparathyroidism (see 146200). Thakker (2001) suggested the designation 'autosomal dominant hypocalcemic hypercalciuria' for this CASR-related disorder. (601198) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: ⁷³ A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.

Disease Ontology ¹¹ Autosomal dominant hypocalcemia 1: An autosomal dominant hypocalcemia disease that has material basis in heterozygous mutation in the calcium sensing receptor gene (CASR) on chromosome 3q21.

Autosomal dominant hypocalcemia: A metal metabolism disorder characterized by autosomal dominant inheritance of variable degrees of hypocalcemia with normal to low levels of parathyroid hormone.

GARD: ¹⁹ A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.

Orphanet: ⁵⁸ A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.

Clinical features from OMIM®:

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