Bone Abstracts

Background: Infantile hypercalcemia occurs in ~15% of patients with Williams Syndrome (WS) and is typically mild. Severe hypercalcemia has been reported in infants/toddlers with WS, requiring treatment with intravenous (IV) saline hydration, furosemide, calcitonin, calcium and vitamin D restriction, and in some cases IV bisphosphonates.

Presenting problem: Three cases of infants with WS age 9–13 months presented with severe hypercalcemia, failure to thrive, increasing irritability, lethargy, regression of developmental milestones, and hypotonia. All patients had dysmorphic features characteristic of WS with cardiac defects (supravalvular aortic stenosis in 2 and pulmonary stenosis in 1). Initial lab/imaging studies revealed marked hypercalcemia, with serum calcium ranging from 17.2–21.7 mg/dl [4.3–5.4 mmol/l] (normal 8–10.5 mg/dl [2.0–2.6 mmol/l]), low serum phosphorus, suppressed parathyroid hormone, normal 25-hydroxy vitamin D, elevated BUN and creatinine, hypercalciuria, and bilateral medullary nephrocalcinosis on renal ultrasound.

Clinical management: Conventional therapy with saline hydration, furosemide and subcutaneous calcitonin decreased serum calcium levels to some degree, but failed to normalize the calcium levels. Due to persistent hypercalcemia, 2 doses of IV pamidronate (PAM) were given in Patients A and B. Follow up calcium levels have been normal or mildly elevated (10.8 mg/dl [2.7 mmol/l]) in Patient A. In Patient B, rebound hypercalcemia was noted within a month of PAM prompting treatment with zoledronic acid (ZA) at 0.05 mg/kg per dose, with subsequent normocalcemia throughout 2.5 years post-therapy. In Patient C (initial serum calcium of 17.8 mg/dl [4.4 mmol/l]), IV ZA at 0.025 mg/kg per dose was administered after inadequate response to conventional therapy. Calcium levels normalized within 8 hours after ZA, with stable clinical course and shortest hospital stay. Clinical improvement in all areas including general well-being, muscle tone, growth and development was noted in all three patients after hypercalcemia was corrected.

Discussion: Severe hypercalcemia, which requires aggressive therapy, can occur in infants with WS, leading to significant complications including failure to thrive, developmental delay, acute kidney injury and nephrocalcinosis. We report the first successful use of ZA in infants with WS that resulted in rapid and sustained normalization of hypercalcemia. Treatment with ZA should be considered in WS with severe life-threatening hypercalcemia after failed conventional therapy.

Disclosure: The authors declared no competing interests.