Aim: To study the etiology and therapeutic strategy in 3 cases of refractory infantile hypercalcemia, nephrocalcinosis and renal failure.
Background: Williams syndrome (WS) is a systemic multi-organ disorder caused by a 1.5 MB deletion in chromosome 7 encompassing 26-28 genes. While common WS phenotypes such as supravalvular aortic stenosis and dysmorphic facial features have been associated with a specific loss of the ELN gene in the deleted segment, the cause of hypercalcemia, a rare manifestation of these patients remains unknown. Elevated levels of 1,25(OH)2vitaminD have been proposed as a mechanism for WS hypercalcemia.
Methods and results: 3 infants presented with severe infantile hypercalcemia (>14mg/dl). Case1: Constipation associated with azotemia (BUN-17mmol/l, Cr-94 micromol/L) and profound nephrocalcinosis were the clinical presentation of an 18-month-old male. Initial studies showed severe hypercalcemia(15.2). FISH revealed the diagnosis of WS. After several treatment failures pamidronate led to resolution of the hypercalcemia, azotemia and nephrocalcinosis. Case2: A 16-month-old known Williams syndrome patient presented with restlessness, severe hypercalcemia(14.2) and nephrocalcinosis. She was treated successfully with pamidronate. These 2 patients showed low levels of 1,25(OH)2vitaminD.
Case 3: A 6 month old girl presented with diarrhea and FTT. Initial investigation showed hypercalcemia(19) and she was treated with pamidronate. FISH studies are pending.
Conclusion: Williams syndrome may present with renal failure, nephrocalcinosis and GI symptoms (constipation) resulting from hypercalcemia. Hypercalcemia in WS patients is not exclusively related to high levels of 1,25(OH)2vitaminD. Pamidronate is the only safe and effective treatment in these patients. Long term follow up is still warranted.
