Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease that runs a benign course. Its prevalence is not clearly established [
1]. It is important to differentiate it from the much more common primary 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 well as the proliferation of parathyroid cells when the calcium 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 confined to a single family, with only a few having been described in more than one family. Inactivating mutations result in decreased sensing of calcium levels, shifting 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 (CKD), and low vitamin D level. Because two of her children had hypercalcemia and hypocalciuria as well, we carried out DNA sequencing in the
CaSR gene in the patient and three of her children.