Familial hypocalciuric hypercalcemia caused by homozygous CaSR gene mutation: A case report of a family

INTRODUCTION: Familial hypocalciuric hypercalcemia (FHH) is a group of autosomal dominant genetic diseases with persistent hypercalcemia and hypocalciuria. The calcium-sensitive receptor (CaSR) plays an important role in calcium and phosphorus metabolism. PATIENT CONCERNS: A 32-year-old man who had diabetes was admitted to our hospital due to poor glycemic control, and was found to have hypercalcemia, hypophosphatemia, and hyperparathyroidism. Single-Photon Emission Computed Tomography (SPECT) (99-mTcMIBI) examination result was negative. The result of 24-h urine calcium was 2.18 mmol/24 h, and the 24-h urinary calcium to creatinine ratio (UCCR) was 0.006. Family survey showed that all of the family members had hypercalcemia. DIAGNOSIS: The CaSR gene mutation study revealed that the proband had a homozygous mutation for a T>C nucleotide substitution at c.1664 in exon 6, while both the mother and the father had heterozygous mutations at the same site of exon 6. The clinical diagnosis was considered to be FHH type1. INTERVENTIONS: The patient was treated with conventional calcium-lowering therapy which was not effective. Cinacalcet was suggested but not used. The patient received salmon calcitonin nasal spray and furosemide tablets treatment for 1 month after discharge, and then stopped the medication. OUTCOMES: On follow up 4 months after being discharged, the serum calcium level was 3.18 mmol/L, and the PTH level was 275.4 ng/mL. He had felt fatigued, intermittent abdominal pain and lost 3.9 kg of weight. CONCLUSION: This case studied a family with FHH, and the CaSR gene c.1664T>c mutation was the possible pathogenic cause. If parathyroid location examination is unclear for hyperparathyroidism, the possibility of FHH should be considered. For FHH patients, conventional calcium reduction therapy was ineffective and parathyroid surgery cannot alleviate their hypercalcemia.