This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by RAJALA, M. M. Articles by HEATH, H. Search for Related Content PubMed PubMed Citation Articles by RAJALA, M. M. Articles by HEATH, H., III

Distribution of Serum Calcium Values in Patients with Familial Benign Hypercalcemia (Hypocalciuric Hypercalcemia): Evidence for a Discrete Genetic Defect^*

MARY M. RAJALA and HUNTER HEATH, III

Mayo Medical School and the Endocrine Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, Mayo Clinic Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dr. Hunter Heath III, Mayo Clinic, 5-164 West Joseph Building, Rochester, Minnesota 55905.

One group has reported hypocalcemic individuals in families affected with familial benign hypercalcemia (FBH), suggesting either that FBH is merely an extreme of normality or that hypocalcemia is independently inherited in that kindred. To test these hypotheses, we examined the distributions of serum total calcium (Ca) values in 260 normal adults and 171 adult individuals in 21 FBH kindreds. We excluded from analysis the 21 adult probands, leaving 85 apparently affected persons (Ca, >10.1 mg/dL or >2.52 mmol/L) and 65 apparently unaffected individuals (Ca, 10.1 mg/dL or 2.52 mmol/L). Five FBH family members were hypocalcemic (<8.9 mg/dL or <2.22 mmol/L); of these, 3 had hypoproteinemia or hypoalbuminemia, 1 had surgical hypoparathyroidism, and 1 was pregnant (and thus excluded from further analysis). Histogram analysis suggested a bimodal distribution of Ca in the FBH families, and familial serum Ca levels were significantly elevated (P < 0.001, rank sum). When only apparently unaffected family members were compared with normal individuals with serum Ca of 10.1 mg/dL or 2.52 mmol/L or less, the distributions were virtually identical. Our results indicate that hypocalcemia in members of families with FBH is of sporadic nongenetic origin. Furthermore, FBH is not an extreme of the normal distribution, but, instead, a clear disturbance with its own distribution about a supranormal mean serum calcium value.

^* This work was supported in part by grants from the USPHS, NIH (RR-585 and AM-32526).

NIH Summer Student Research Fellow (T35-HL-07551).

Received May 1, 1987.