HDCN Article Review/Hyperlink

Pearce SHS, Williamson C, Kifor O, Bai M, Coulthard MG, et al

A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor

New Engl J Med (Oct) 335:1115-1122 1996

Serum calcium is controlled by many factors, including the circulating level of PTH, and renal excretion as modulated by PTH. The release of PTH is in turn regulated via the serum calcium level by way of a calcium sensing receptor. Genetic abnormalities of the calcium receptor have now been described. When the receptor is hypoactive, PTH levels fail to be suppressed, PTH levels are high, and familial hypercalcemia with hypocalciuria result. In this paper, the mirror image genetic aberration is described, caused when the receptor is hypersensitive to external calcium. It shuts off PTH too soon, causing hypocalcemia and hypercalciuria, although PTH levels are only borderline low or in the normal range. The calcium sensing receptor is also expressed in the kidney, and in its mutated form, altered sensitivity may be directly responsible for the hypercalciuria and perhaps even primarily, for the hypocalcemia.

What implications does this have for treatment? Hypocalcemia associated with idiopathic hypoparathyroidism responds well to vitamin D treatment. Wih the presently described receptor mutation, in which calcium receptor sensitivity is heightened, however, nephrocalcinosis and renal calculi are common. As most of the patients will have been treated with vitamin D, it is possible that vitamin D therapy may have exacerbated the nephrocalcinosis. More data here are required, and in the meantime, vitamin D therapy should be given prudently to such patients, to raise serum Ca not to the normal range, but just high enough to relieve symptoms. (John T. Daugirdas, M.D., University of Illinois at Chicago)

The abstract of this paper is available from the National Library of Medicine's PubMed site: click here .

For accompanying editorial by Dr. David Heath: Click here.