Colin P Hawkes1,2, Sani M Roy3, Bassem Dekelbab4, Britney Frazier5, Monica Grover6, Jaime Haidet7, James Listman8, Sarianne Madsen9, Marian Roan10, Celia Rodd11, Aviva Sopher12, Peter Tebben13, Michael A Levine1,2. 1. Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Division of Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, Texas. 4. Division of Endocrinology and Diabetes, Beaumont Children's, Royal Oak, Michigan. 5. Multicare Mary Bridge Children's Hospital and Health Center, Tacoma, Washington. 6. Division of Pediatric Endocrinology, Stanford University, Stanford, California. 7. Center for Diabetes and Endocrinology, Akron Children's Hospital, Akron, Ohio 44308. 8. Pediatric Nephrology Group, Albany Medical College, Albany, New York. 9. UCSF Benioff Children's Hospital, San Francisco, California. 10. Department of Clinical Nutrition, UCSF Benioff Children's Hospital, Oakland, California. 11. Department of Pediatrics and Child Health, The Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. 12. Division of Pediatric Endocrinology Diabetes and Metabolism, Columbia University Irving Medical Center, New York, New York. 13. Division of Pediatric Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
Abstract
CONTEXT: The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. OBJECTIVE: To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. DESIGN: A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally. RESULTS: There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia. CONCLUSIONS: Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
CONTEXT: The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. OBJECTIVE: To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. DESIGN: A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally. RESULTS: There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia. CONCLUSIONS:Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
Authors: Cynthia St Hilaire; Shira G Ziegler; Thomas C Markello; Alfredo Brusco; Catherine Groden; Fred Gill; Hannah Carlson-Donohoe; Robert J Lederman; Marcus Y Chen; Dan Yang; Michael P Siegenthaler; Carlo Arduino; Cecilia Mancini; Bernard Freudenthal; Horia C Stanescu; Anselm A Zdebik; R Krishna Chaganti; Robert L Nussbaum; Robert Kleta; William A Gahl; Manfred Boehm Journal: N Engl J Med Date: 2011-02-03 Impact factor: 91.245
Authors: D A Fraser; J Thoen; S Bondhus; M Haugen; J E Reseland; O Djøseland; O Førre; J Kjeldsen-Kragh Journal: Clin Exp Rheumatol Date: 2000 Mar-Apr Impact factor: 4.473