Ketotic hypercalcemia: A case series and description of a novel entity

Context: The ketogenic diet is increasingly used in refractory epilepsy and is associated with clinically significant effectsonboneandmineral metabolism. Although hypercalciuriaandloss ofbone mineral density are common in patients on the ketogenic diet, hypercalcemia has not previously been described. Objective: The aim of the study was to describe three childrenwhodeveloped hypercalcemia while on the ketogenic diet. Design: A retrospective chart review of three children on the ketogenic with severe hypercalcemia was conducted. Results: We describe three children on the ketogenic diet for refractory seizures who presented with hypercalcemia. Case 1 was a 5.5-year-old male with an undiagnosed, rapidly progressive seizure disorder associated with developmental regression. Case 2 was a 2.5-year-old male with a chromosomal deletion of 2q24.3, and case 3 was a 4.6-year-old male with cerebral cortex dysplasia. Patients had been on a ketogenic diet for 6 to 12 months before presentation. Daily intake of calcium and vitaminDwas not excessive, and all three patients were not acidotic because they were taking supplemental bicarbonate. Each child had elevated serum levels of calcium and normal serum phosphate levels, moderately elevated urinary calcium excretion, and low levels of serum alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D. All patients responded to calcitonin. Conclusions: Hypercalcemia is an uncommon complication of the ketogenic diet, and these children may represent the severe end of a clinical spectrum of disordered mineral metabolism. The mechanism for hypercalcemia is unknown but is consistent with excess bone resorption and impaired calcium excretion.