The role of the extracellular calcium-sensing receptor in health and disease.
The calcium-sensing receptor has a key role in calcium homeostasis, it is involved in the regulation of the serum calcium level within minutes via the secretion and action of parathyroid and the excretion of calcium in the kidney in a negative feedback manner. Mutations of the calcium sensing receptor gene leads to inactivating and activating mutations resulting in diseases with hypercalcaemia and hypocalcaemia. The loss of function mutations are associated with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant disease characterised by lifelong mild hypercalcaemia, low urinary calcium excretion, and inappropriate high parathyroid hormone levels, sometimes difficult to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with FHH did not profit from parathyroidectomy, a calcium lowering therapy is not necessary. The gain of function mutations of the calcium-sensing receptor are associated with autosomal dominant hypocalcaemia (ADH), a disease characterised by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium excretion and normal PTH levels. A therapy to raise the serum calcium concentration has to be done carefully and is only indicated in symptomatic patients, because of enhancement of hypercalciuria with the risk of nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium sensing receptor gene facilitates the sometimes difficult diagnosis. The development of compounds modulating the calcium sensing receptor function and thereby the section of PTH may become an important role in treatment of diseases of calcium metabolism.
Raue
F
F
Molecular genetic laboratory, endocrine practice, Heidelberg, Germany. friedhelm.raue@taue-endokrinologie.de
Haag
C
C
Schulze
E
E
Frank-Raue
K
K
D000328:Adult; D002118:Calcium / Q000652:urine; D006801:Humans; D006934:Hypercalcemia / Q000503:physiopathology; D006961:Hyperparathyroidism / Q000151:congenital / Q000503:physiopathology; D006996:Hypocalcemia / Q000503:physiopathology; D007011:Hypoparathyroidism / Q000503:physiopathology; D007231:Infant, Newborn; D007668:Kidney / Q000502:physiology*; D044169:Receptors, Calcium-Sensing / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D044169:Receptors, Calcium-Sensing; D002118:Calcium