No abstract

Background: Familial hypocalciuric hypercalcemia (FHH) is usually characterized by asymptomatic hypercalcemia, hypocalciuria and normal PTH. The diagnosis of FHH is often incidental and seldom require any medical intervention. Patient description: We are reporting Case 1 an 8 years old female incidentally diagnosed with hypercalcemia at the age of 3 years. She had complaints of constipation, polyuria and nocturia. Urinary calcium excretion was extremely low. A trial of Cinacalcet was initiated at 7 years of age, which provided completes symptomatic relief, increased urinary calcium excretion and decreased serum calcium levels. Case 2 is a 7 year old male was evaluated for leg cramps and high serum calcium level (11.3 mg/dL). The patient complained of occasional leg pains. Case 3 is a 6 year old boy the younger brother of Case 2 was referred for high serum calcium level (11.1 mg/dL). Family history is significant for hypercalcemia in their father. After confirmation of a CaSR mutation, both were started on Cinacalcet 30mg twice a day. Over the course of treatment the calcium levels were normalized and leg pain resolved in case 2. Result: Mutation analysis of the CASR gene in case 1 revealed a missense mutation (CGA-CAA, R185Q). In case 2 and case 3 a heterozygous mutation (GCC->ACC, A194T) was found in the extracellular domain in the CaSR encoded by exon 4. Conclusion: We are reporting a novel mutation of CaSR in a severe presentation in case 1 and lack of symptoms in parents would suggest a de-novo mutation. In cases 2 and 3 the mutation was probably inherited from the father, consistent with autosomal dominant pattern of inheritance of FHH. The use of Cinacalcet successfully improved calcium levels and alleviated all the associated symptoms.