A NOVEL MUTATION IN CALCIUM-SENSING RECEPTOR PRESENTING AS FAMILIAL HYPOCALCIURIC HYPERCALCEMIA IN A YOUNG MAN.

OBJECTIVE

Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by elevated serum calcium with relatively low urinary calcium excretion. It typically results from an altered set point in calcium homeostasis originating from mutations in the calcium-sensing receptor (), , or genes, which encode for the calcium-sensing receptor (CaSR), adaptor-related protein complex 2, and G-protein alpha-11 subunit, respectively. Despite numerous reports of novel variants in these genes associated with FHH, new variants continue to be discovered.

METHODS

We describe a 20-year-old man with a family history of hypercalcemia who had clinical findings compatible with FHH and no evidence of multiple endocrine neoplasia who underwent gene sequencing for evaluation of hypercalcemia. Parathyroid gland single-photon emission computerized tomography scan was normal.

RESULTS

gene sequencing revealed a previously unreported heterozygous intronic variant at position 1608+3A>G (chromosome 3: 121994892) resulting in a 77-residue deletion. His mother has a history of bipolar disorder and hyperparathyroidism with an adenoma found on imaging, yet our patient had no evidence of adenoma and therefore no surgical intervention was recommended. Given that CaSR plays a role in parathyroid growth, some variants in may ultimately lead to parathyroid hypertrophy and be mistaken for primary hyperparathyroidism.

CONCLUSION

Long-term clinical follow up will be helpful in understanding the ultimate effects of specific mutations on parathyroid growth or progression to significant hypercalcemia.