Familial hypocalciuric hypercalcemia is a condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.
Most cases are associated with loss of function mutations in the CaSR gene, which encodes a calcium-sensing receptor, expressed in parathyroid and kidney tissue. The perceived lack of calcium levels by the parathyroid leads to constitutively high levels of parathyroid hormone, and therefore hypercalcemia. Functionally, parathyroid hormone (PTH) (aka parathormone or parathyrin) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate.
Another form has been associated with chromosome 3q.
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.
No treatment is generally required, as bone demineralisation and kidney stones are relatively uncommon in the condition.
Functions of the Calcium-sensing Receptor
- Parathyroid gland: mediates negative feedback mechanisms relating to PTH secretion (PTH secretion should decrease if there is a high blood calcium level). Abnormalities in the CaSR here cause hypercalcaemia.
- Kidneys: mediates negative feedback mechanisms relating to calcium reabsorption from the tubular system (reabsorption should decrease if there is a high blood calcium level). Abnormalities in the CaSR here cause both hypercalcaemia and hypocalciuria.
- Most cases: Asymptomatic (unlike primary hyperparathyroidism)
- Hypocalciuria ( 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)