Familial hypocalciuric hypercalcemia with a de novo heterozygous mutation of calcium-sensing receptor

[摘要] A de novo heterozygous inactivating mutation of calcium-sensing receptor (CASR) gene typically causes neonatalhyperparathyroidism (NHPT) with moderate hypercalcemia and hyperparathyroid bone disease. We present a case ofasymptomatic hypocalciuric hypercalcemia with a de novo heterozygous mutation in CASR, S591C, which is primarilyreported to be responsible for NHPT. A 54-year-old female was referred for investigation of asymptomatic hypercalcemia thatwas initially found in the 1980s but without a history of bone disease during the perinatal period. She had moderatehypercalcemia (12.4 mg/dl) and relative hypocalciuria (fractional extraction of calcium 1.07%) but normal intact parathyroidhormone and serum 1,25-dihydroxyvitamin D3. Pedigree analysis revealed that she carried a de novo heterozygous mutationof S591C, which she transmitted to an affected child with moderate hypercalcemia but not to other children, who had normalserum calcium levels. A de novo heterozygous CASR mutation that is responsible for NHPT may also present in individualswith asymptomatic hypocalciuric hypercalcemia. Caution is required when predicting course and outcome in a pedigree withCASR mutation, as well as incidental hypercalcemia, because of its variable phenotypes.

[学科分类] 血液学

[关键词] Adult;Female;Asian - Japanese;Parathyroid;Bone/calcium;Familial hypocalciuric hypercalcemia;CASR gene mutation;Hypercalcemia;Hypocalciuria;Calcium (serum);phosphate (serum);calcium (urine);radionuclide imaging;sestamibi scan;genetic analysis;PTH;Genetics;Unique/unexpected symptoms or presentations of a disease;May;2015