Familial Hypocalciuric Hypercalcemia: A Novel Mutation

Presentation Number: MON 305
Date of Presentation: April 3rd, 2017

Heather Greenberg*1 and Julie Probst-Riordan2
1NYU Langone Medical Center, New York, NY, 2NYU Langone Medical Center


Familial hypocalciuric hypercalcemia (FHH) is a rare but benign disease. Currently, more than 130 mutations of the calcium sensing receptor (CaSR) are known. Most mutations occur in the extra-membrane domain, where ionized calcium binds. Clinically, patients rarely suffer any complications, since the hypercalcemia is mild. The condition can often be confused with primary hyperparathyroidism (PHPT) because of the elevation of parathyroid hormone (PTH) and associated hypercalcemia. Here we describe a case of mild, asymptomatic hypercalcemia with elevated PTH with a subsequent diagnosis of FHH and a novel mutation of the CaSR.

A 64-year-old male with a medical history of hypertension and alcohol abuse complicated by chronic pancreatitis was admitted for observed medical therapy for multi-drug resistant tuberculosis. Biochemical testing noted a mild asymptomatic hypercalcemia (serum calcium of 10.9 mg/dl). He denied any history of hypercalcemia. He had no history of nephrolithiasis, constipation, dehydration, confusion, body aches, osteoporosis or fractures. Initial laboratory work revealed an intact PTH of 49.0 pg/ml, 25 OH vitamin D of 17.8 ng/ml, and 1,25 OH vitamin D of 22.1 pg/nl. Twenty-four-hour urine for calcium was very low at 34 mg/24 hr (2300 ml with a urinary creatinine of 0.7 mg/24h) with a calcium excretion of <0.003. It was thought that vitamin D deficiency could be contributing to his low urinary calcium, and the patient was treated for one month with ergocalciferol 50,000 units weekly. A repeat 25 OH vitamin D level after one month of therapy was 34.6 ng/ml and a repeat 24 hr urine for calcium remained low at 37 mg/24 hr. Genetic testing of the CASR was sent due to high suspicion for FHH and revealed a novel missense mutation at residue 69 (Arg to Cys) of the extra-membrane domain.

At initial evaluation, this patient appeared to have other more common etiologies of hypercalcemia such as PHPT or his granulomatous disease. However, after 24 hr urine for calcium remained low despite vitamin D repletion, suspicion was raised for FHH. Although patients with PHPT can have a low 24 hr excretion of calcium, it is usually not <0.02, which is common in FHH (80% of cases). Several other factors can help differentiate between FHH and PHPT; personal history of mild to moderate hypercalcemia, kidney stones, osteoporosis, as well as family history of calcium disorders.

This case illustrates an interesting presentation of asymptomatic hypercalcemia which could have easily been confused for PHTP. Instead, this patient has FHH with a novel mutation of the CaSR. It is important to make the diagnosis of FHH when suspected in order to avoid parathyroidectomy. Misdiagnosis can lead to unnecessary surgery and even permanent hypoparathyroidism in complicated cases.


Nothing to Disclose: HG, JP