Endocrine Abstracts

Introduction: Familial hypocalciuric hypercalcemia (FHH) is an autosomal-dominant genetic disease caused by an inactivating mutation in the gene encoding the calcium sensing receptor (CaSR). The loss of function leads to increased circulating level of PTH and subsequent hypercalcemia.

Case report: 20-year-old male patient referred to our center with hypercalcemia which was found after the syncope. His serum calcium level was 11.7 mg/dl and the phosphorus was 2.4 mg/dl (normal: 2.5–4.5). The serum PTH was 131 pg/ml (normal: 10–65), 25-hydroxyvitamin D3: 12.2 ng/ml and 24-h urine calcium excretion was below 200 mg/day. His calcium/creatinine clearance ratio was 0.005. After replacement of vitamin D, calcium/creatinine clearance ratio was still < 0.01. The family screening planned for FHH. Both his 49 year-old father and 22 year-old brother had also slightly elevated PTH in spite of moderately increased serum calcium levels. Their calcium/creatinine clearance ratios were <0.01. Patient is tested for mutations in the CaSR gene. The patient was found to have a heterozygous missense mutation (p.Ser182Pro/c.544T >C) in the CaSR gene, suggesting the diagnosis of FHH. This mutation has never been reported in literature or in the Human Gene Mutation Database. In the follow up of the patient 30 mg/day cinacalcet treatment was started and increased up to 60 mg/day due to the persistant symptomatic hypercalcemia. Plasma calcium levels were normalized and PTH levels decreased slightly after the treatment.

Conclusions: FHH is a rare disorder, but it is clinically important because it can be confused with asymptomatic primary hyperparathyroidism. FHH is usually asymptomatic but rarely symptoms of fatigue, weakness, and excessive thirst and concentration problems are experienced. Cinacalcet is potentially a useful treatment of patients with intractable hypercalcemia caused by mutations in the CaSR gene.