Severe Hypercalcemia in an Infant With Transient Disaccharidase Deficiency

A previously healthy 11-month-old, full-term female developed growth failure, feeding intolerance, and irritability starting at 10 months of age. She was found to have a serum calcium level of 3.75 mmol/L (15 mg/dL) (reference range, 2.13-2.62 mmol/L; 8.5-10.5 mg/dL), consistent with severe hypercalcemia. She had bilateral nephrocalcinosis. Hypercalcemia improved with intravenous fluid hydration, but calcium rose again once intravenous fluids were discontinued and while consuming a low-calcium diet. Laboratory tests for common causes of hypercalcemia were negative. Stool-reducing substances were positive on 2 occasions. Endoscopic biopsy confirmed low disaccharidase levels. Her diet was changed to disaccharide-free formula, and hypercalcemia resolved. Genetic testing for congenital disaccharidase deficiency was negative. After repeat endoscopy demonstrating improved disaccharidase levels, disaccharides were incrementally reintroduced to the diet and calcium levels remained normal. This case demonstrates that disaccharidase deficiency, a rare inborn error of metabolism associated with hypercalcemia, may be a transient cause of hypercalcemia. The mechanism of hypercalcemia remains unknown.