Hypocalciuric hypercalcemia- familial- type 2


Familial benign hypercalcemia, type 2
Hypercalcemia, familial benign type 2
Hypocalciuric hypercalcemia, familial, type 2
Familial hypocalciuric hypercalcemia


A rare genetic disorder known as familial hypocalciuric hypercalcemia causes an increase of calcium in your blood because of faulty calcium receptors in your body. Treatment is typically considered unnecessary because it is a benign condition. FHH can be difficult to distinguishfrom primary hyperparathyroidism, for which parathyroidectomy is typically performed; individuals with FHH are typically advised to avoid parathyroidectomy.

In the medical literature, some authors reference different types of familial hypocalciuric hypercalcemia (FHH) - types 1, 2 and 3. These subtypes of FHH are generally used to describe forms of the condition that are genetically distinct (i.e. are caused by mutations in different genes). In more than 65% of families affected by FHH, the condition is due to mutations in the CASR gene, which is located on chromosome 3. In the other families affected by FHH, the exact genetic abnormality that causes the condition has not yet been identified. Researchers have discovered that one of two other genes, located at different parts of chromosome 19, may be responsible for the condition in some of these remaining individuals. These three genetically distinct types of FHH have therefore been designated as FHH type 1 (due to a mutation in the CASR gene at chromosome 3q21.1) and FHH types 2 and 3 (due to genetic abnormalities at chromosome locations 19p and 19q13, respectively).


  • Kidneys: Excess calcium in your blood means your kidneys have to work harder to filter it out. This can cause excessive thirst and frequent urination.
  • Digestive system: Hypercalcemia can cause stomach upset, nausea, vomiting and constipation.
  • Bones and muscles: In most cases, the excess calcium in your blood was leached from your bones, which weakens them. This can cause bone pain. Some people who have hypercalcemia also experience muscle weakness.
  • Brain: Hypercalcemia can interfere with the way your brain works, resulting in confusion, lethargy and fatigue.
  • High serum parathyroid level 
  • Increased risk of gallstones
  • Excessive thirst (Polydipsia)
  • Asymptomatic


FHH type  2 is due to loss-of-function mutations of the genes GNA11 on chromosome 19p13.

Hypercalcemia may be also caused by:

  • Overactive parathyroid glands. The most common cause of hypercalcemia, overactive parathyroid glands (hyperparathyroidism) may stem from a small noncancerous tumor on one or more of the four parathyroid glands.
  • Cancer. Lung cancer and breast cancer, as well as some cancers of the blood, can increase your risk of hypercalcemia. Spread of cancer (metastasis) to your bones also increases your risk of hypercalcemia.
  • Other diseases. Certain diseases, such as tuberculosis and sarcoidosis, may raise blood levels of vitamin D, which stimulates your digestive tract to absorb more calcium.
  • Immobility. People with cancer or other diseases that cause them to spend a great deal of time sitting or lying down may develop hypercalcemia. Over time, bones that don't bear weight release calcium into the blood.
  • Medications. Certain drugs — such as lithium, which is used to treat bipolar disorder — may increase the release of parathyroid hormone.
  • Supplements. Taking excessive amounts of calcium or vitamin D supplements over time can raise calcium levels in your blood above normal.
  • Hereditary factors. A rare genetic disorder known as familial hypocalciuric hypercalcemia causes an increase of calcium in your blood because of faulty calcium receptors in your body.
  • Dehydration. A common cause of mild or transient hypercalcemia is dehydration, because when there is less fluid in your blood, calcium concentrations rise.


If you develop hypercalcemia, it may be possible to prevent bone and kidney damage by doing the following:

  • Drink plenty of fluids, especially water. Drinking fluids can help keep you from dehydration and help prevent kidney stones from forming.
  • Exercise. Once your calcium levels return to normal, and if you're otherwise healthy, it's important to remain active to help maintain bone density. Try to combine strength training with weight-bearing exercises.
  • Don't smoke. Smoking has been shown to increase bone loss as well as dramatically increase your risk of a number of serious health problems. Talk to your doctor about the best ways to quit.


Affected individuals usually do not have any signs or symptoms of the condition, and hypercalcemia is often diagnosed incidentally. In some individuals, weakness, fatigue, thought disturbance, and/or excessive thirst (polydipsia) have been reported

Because hypercalcemia may cause few, if any, signs or symptoms, you may not know you have the disorder until routine blood tests show a high level of blood calcium. Blood tests also can reveal whether your parathyroid hormone level is high, indicating that you have hyperparathyroidism.

To determine if your hypercalcemia is caused by an underlying problem, such as cancer or sarcoidosis, your doctor might recommend imaging tests of your bones or lungs.


If your hypercalcemia is mild, you and your doctor may choose to watch and wait, monitoring your bones and kidneys over time to be sure they remain healthy.

Possible medications:

  • Calcimimetics. This type of drug mimics calcium circulating in the blood, so it can help control overactive parathyroid glands.
  • Bisphosphonates. Intravenous osteoporosis drugs can help rebuild bone weakened by hypercalcemia. Risks associated with this treatment include osteonecrosis of the jaw and certain types of thigh fractures. Zoledronate/Zoledronic acid (Zometa) is a FDA approved orphan drug  for the treatment of hypercalcemia induced by tumors.
  • Prednisone. If your hypercalcemia is caused by high levels of vitamin D, short-term use of steroid pills such as prednisone might be helpful.
  • IV fluids and diuretics. Extremely high calcium levels can be a medical emergency. Hospitalization for treatment with IV fluids and diuretics to promptly lower the calcium level may be needed to prevent heart rhythm problems or damage to the nervous system.


Problems associated with overactive parathyroid glands often can be cured by surgery to remove the malfunctioning tissue. In many cases, only one of a person's four parathyroid glands is affected. A special scanning test uses an injection of a small dose of radioactive material to locate the gland or glands that aren't working properly.


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