Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium

被引:48
作者
Brown, EM
机构
[1] Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Membrane Biol Program, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Med, Boston, MA USA
关键词
D O I
10.1016/S0889-8529(05)70148-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
An extracellular calcium (Ca-o(2+))-sensing receptor (CaR) recently cloned from the parathyroid gland mediates the direct actions of Ca-o(2+) on parathyroid, kidney, and other tissues, playing key roles in systemic Ca-o(2+) homeostasis. Disorders in which there is generalized resistance to the usual actions of Ca-o(2+) on these latter issues results from inactivating mutations in the CaR. In the heterozygous state, inactivating mutations usually cause a generally asymptomatic condition characterized by mild parathyroid hormone (PTH)-dependent hypercalcemia accompanied by relative hypocalciuria, known as familial hypocalciuric hypercalcemia (FHH). A much more severe form of hypercalcemia in neonates, neonatal severe hyperparathyroidism (NSHPT), arises from homozygous inactivating mutations of the CaR, or in occasional cases, from heterozygous mutations-perhaps because specific mutations exert a dominant negative action on the wild-type CaR in the latter cases. In primary hyperparathyroidism (PHPT) and in some cases of severe uremic secondary hyperparathyroidism (SHPT), there is selective resistance of pathological parathyroid glands to Ca-o(2+) in the absence of inactivating the CaR mutations, that occurs in part because the level of expression of the receptor is reduced. Thus PTH-forms of hypercalcemia can result from either inherited, generalized Ca-o(2+) resistance ranging in severity from mild to severe, as in FHH or NSHPT, respectively, or from acquired, tissue (i.e., parathyroid)-specific resistance to Ca-o(2+) in PHPT and SHPT.
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页码:503 / +
页数:21
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