title: Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene.
abstract: The calcium-sensing receptor (Ca-R) is a G-protein-coupled surface receptor that plays a crucial role in calcium homeostasis via parathyroid hormone secretion. Mutations of this receptor can cause a gain in, or loss of, function, leading to hypo- or hypercalcemia, respectively. We report here a family with hypocalcemia in whom a heterozygous missense mutation in exon 4 was demonstrated, predicting a proline to leucine substitution (P221L) in the extracellular part of the Ca-R. Clinical symptoms were limited to fatigue. When serum calcium was further lowered via a citrate infusion, a significant increase in circulating iPTH was observed, although with lower peak values than in normal controls, suggesting a gain in function of the Ca-R. Treatment with calcium supplements and calcitriol led to prohibitive hypercalciuria without normalizing serum calcium. The aims of this case report are: (1) to present a mutation in the Ca-R with a gain in function at a codon where previously loss of function was described, and (2) to suggest that measuring circulating iPTH during a citrate infusion in the presence of familial hypocalcemia is an additional test to diagnose this particular form of hypoparathyroidism.
authors.affiliation: Department of Endocrinology, Vrije Universiteit Brussel (AZ-VUB), Laarbeeklaan 101, 1090, Brussels, Belgium
authors.forename: K
authors.initials: K
authors.lastname: Poppe
authors.forename: R
authors.initials: R
authors.lastname: Karmali
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: L
authors.initials: L
authors.lastname: Vanhaelst
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
authors.forename: M
authors.initials: M
authors.lastname: Fuss
authors.forename: B
authors.initials: B
authors.lastname: Velkeniers