Elamin and de Buyl Journal of Medical Case Reports 2010, 4:349 http://www.jmedicalcasereports.com/content/4/1/349 C A S E R E P O R T JOURNAL OF MEDICAL CASE REPORTS Open Access A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report Wael F Elamin1,2*, Olivier de Buyl1 Abstract Introduction: Familial hypocalciuric hypercalcemia is a rare autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia due to mutations of the calcium-sensing receptor gene. Disorders of calcium metabolism are very common in the elderly, and they can coexist with familial hypocalciuric hypercalcemia in affected families. Case presentation: We describe an Irish family with hypercalcemia and hypocalciuria. The proband, an 80-year-old Irish woman, presented with hypercalcemia, relative hypocalciuria, and an elevated parathormone level. She also had chronic kidney disease stage 3 and vitamin D deficiency. Two of her sons were also found to be hypercalcemic and hypocalciuric. DNA sequencing identified a novel missense inactivating mutation in the calcium sensing-receptor gene of the proband and her two hypercalcemic sons. Conclusion: Familial hypocalciuric hypercalcemia due to a novel mutation in the calcium-sensing receptor gene was diagnosed in the proband and her two sons. Disorders of calcium metabolism can be multifarious in the elderly. We suggest that testing first degree relatives for calcium levels and DNA sequencing may have a role in the assessment of elderly patients with parathormone-related hypercalcemia. Introduction Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease that runs a benign course. Its prevalence is not clearly established [1]. It is impor- tant to differentiate it from the much more common pri- mary hyperparathyroidism (PHPT) to avoid unnecessary and potentially harmful parathyroidectomy [2]. It has been shown to result from heterozygous inactivating mutations in the calcium-sensing receptor (CaSR) gene in the majority of cases [3]. The calcium sensing receptor (CaSR) is a G-protein-coupled receptor of 1078 amino acids (AAs) with a large extracellular domain and the characteristic seven-transmembrane domains [4]. It is expressed in the parathyroid gland, kidneys, bones, and other tissues [5] and plays a key role in the maintenance of constant levels of extracellular ionized calcium. It modulates the function of chief cells of the parathyroid gland, stimulating the synthesis and secretion of PTH as * Correspondence: wael@elamin.net 1Bantry General Hospital, Bantry, Co. Cork, Ireland Full list of author information is available at the end of the article well as the proliferation of parathyroid cells when the cal- cium level is low, and inhibiting these functions when the calcium level is high. In the kidneys, the CaSR decreases calcium reabsorption, increases calciuresis, and decreases the concentrating ability of the kidney when sensing hypercalcemia, through its effect on the thick ascending limb of the loop of Henle and on the medullary collecting ducts [6]. Two hundred and twenty-three mutations for the CaSR gene are listed in the CaSR mutation database [7]. Of these, 154 are inactivating (loss-of-function), and most of them cause FHH in heterozygous and neonatal severe hyperparathyroidism (NSHPT) in homozygous patients [3]. Curiously, most of these mutations are con- fined to a single family, with only a few having been described in more than one family. Inactivating muta- tions result in decreased sensing of calcium levels, shift- ing the calcium-PTH curve and the set-point to the right [6]. Elderly patients are frequently affected with disorders of calcium metabolism [8-10]. Here we describe an Irish family in which the proband is an octogenarian with hypercalcemia, hypocalciuria, chronic kidney disease © 2010 Elamin and de Buyl; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.