Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene.

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.

Pearson marrow pancreas syndrome: a molecular study and clinical management.

Human mitochondrial DNA (mt DNA) lesions can cause a heterogeneous group of mitochondrial degenerative disorders. We report on a 5-year-old patient suffering from the full-blown picture of Pearson syndrome. His symptoms started in the first year of life with failure to thrive, followed by chronic diarrhoea and lactic acidosis at 18 months of age. Analysis of mitochondrial DNA revealed large amounts of mt DNA molecules with a 2.7 kb deletion in all tissues examined. The diagnosis of Pearson syndrome was made initially in the absence of haematological disturbances. In the following months neutropenia, sideroblastic anaemia and hypoparathyroidism developed. Daily administration of dichloroacetate (DCA) and bicarbonate controls the lactic acidosis, while episodic treatments with filgastrim (Neupogen) reverse episodes of severe neutropenia. Calcium and vitamin D supplementation compensate for the hypoparathyroidism. Chronic administration of DCA and supportive treatment for a long period help to stabilize patients with multiorgan dysfunction.