Causes

Types include:

Name	OMIM	Locus	Gene
HHC1		3q13.3-q21	CASR Calcium-sensing receptor The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
HHC2		19p13.3	?
HHC3		19q13	?

Most cases are associated with loss of function mutations in the CASR

Calcium-sensing receptor

The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...

 gene, which encodes a calcium-sensing receptor

Calcium-sensing receptor

The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...

, expressed in parathyroid

Parathyroid gland

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...

 and kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 tissue. The perceived lack of calcium levels by the parathyroid leads to constiutely high levels of parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

, and therefore hypercalcemia.

Another form has been associated with chromosome 3q.

Differential diagnosis

This condition is indicated by the presence of hypercalcemia (elevated levels of calcium in the blood) at the same time with hypocalciuria (low levels of calcium in the urine). (Usually elevated calcium levels in the blood are correlated with elevated calcium urine levels, as a properly sensing kidney works to excrete the mineral.) A family history could reinforce the diagnosis.

Treatment

No treatment is generally required, as bone demineralisation and kidney stones

Kidney stone

A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...

 are relatively uncommon in the condition.

Functions of the Calcium-sensing Receptor

• Parathyroid gland
  Parathyroid gland
  The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...
  
  : mediates negative feedback mechanisms relating to PTH
  Parathyroid hormone
  Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
  
   secretion (PTH secretion should decrease if there is a high blood calcium level). Abnormalities in the CASR here cause hypercalcaemia.
• Kidneys
  Kidney
  The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
  
  : mediates negative feedback mechanisms relating to calcium
  Calcium
  Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
  
   reabsorption from the tubular system
  Nephron
  The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
  
   (reabsorption should decrease if there is a high blood calcium level). Abnormalities in the CASR here cause both hypercalcaemia and hypocalciuria.

Clinical features

• Most cases: Asymptomatic (unlike primary hyperparathyroidism
  Hyperparathyroidism
  Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
  
  )
• Hypercalcaemia
  Hypercalcaemia
  Hypercalcaemia is an elevated calcium level in the blood. . It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists...
  
  
• Hypocalciuria
  Hypocalciuria
  Hypocalciuria is a low level of calcium in the urine. It is a significant risk factor for predicting eclampsia in pregnancy. It is also common in patients with Gitelman syndrome. It is also found in Familial hypocalciuric hypercalcemia....
  
   ( Ca excretion rate < 0.02 mmol/L).
• Normal to high PTH (CaSR mutation causes the parathyroid glands to be less sensitive to serum calcium, resulting in normal to high PTH despite elevated serum calcium)
• Hypermagnesaemia
• Green colored urine