Bone Abstracts

Background: Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant condition with an estimated prevalence of 1 in 78,000. The commonest cause of FHH is inactivating mutations of the calcium-sensing receptor (CASR) gene, with the rest mostly caused by missense mutations of the GNA11 and AP2S1 genes. FHH is characterized by persistent mild-to-moderate hypercalcemia, hypocalciuria with calcium-creatinine clearance ratio ⩽0.01. The disease runs a benign course. Rare complication includes pancreatitis.

Presenting problem: In the first family, the mother and the two daughters were affected. Both daughters were incidentally found to have persistent hypercalcemia, with normal to mild inappropriate elevation of parathyroid hormone (PTH). The calcium-creatinine clearance ratio of the elder sister was 0.01. The second family involved the mother and her daughter. The daughter was incidentally discovered to have hypercalcemia at birth. On retrospect, the mother had history of back pain with small renal stones found on imaging. She was confirmed to have hypercalcemia on subsequent workup. Her calcium-creatinine clearance ratio ranged from 0.005 to 0.02 (The ratio of 0.02 was documented during pregnancy, with an absolute daily calcium excretion of 9.3 mmol per day). The PTH pattern was similar to the first family, but both mother and baby also had concomitant vitamin D deficiency. Both families were genetically confirmed to have FHH.

Clinical management: The diagnosis of FHH hinges on a low calcium-creatinine clearance ratio. Collection of 24-h urine for calculating the ratio is difficult for infants, therefore, to start testing the parent with hypercalcemia, and follow with mutation analysis might be a more practical strategy.

Both mother and baby of the 2^nd family responded to vitamin D supplement without exacerbation of the hypercalcemic state.

Discussion: The first family showed typical features of FHH. For the second family, the incidental finding of nephrolithiasis in the mother highlighted the fact that we should be open-minded for the diagnosis of FHH in hypercalcemic patient despite the atypical presentation of nephrolithiasis. Moreover, Vitamin D deficiency, though uncommon, had been well reported in patients with FHH and should be tested as part of the workup for FHH and treated accordingly.

Disclosure: The authors declared no competing interests.