Familial hypocalciuric hypercalcemia
Familial hypocalciuric hypercalcemia | |
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Classification and external resources | |
Specialty | Lua error in Module:Wikidata at line 446: attempt to index field 'wikibase' (a nil value). |
ICD-10 | E83.5 |
OMIM | 145980 145981 600740 |
DiseasesDB | 1326 |
Patient UK | Familial hypocalciuric hypercalcemia |
MeSH | D006934 |
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.
Contents
Causes
Types include:
Name | OMIM | Locus | Gene |
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HHC1 | 145980 | 3q13.3-q21 | CaSR |
HHC2 | 145981 | 19p13.3 | ? |
HHC3 | 600740 | 19q13[1] | ? |
Most cases are associated with loss of function mutations in the CaSR gene, which encodes a calcium-sensing receptor,[2] 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) (a.k.a. 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.[3]
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 are relatively uncommon in the condition.[4]
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.
Clinical features
- Most cases: Asymptomatic
- Hypercalcaemia
- 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)
- Hypermagnesaemia