Joost Hoenderop, René Bindels and international colleagues published an article in the New England Journal of Medicine

Joost Hoenderop and Rene Bindels

Joost Hoenderop and René Bindels published together with colleagues from Germany, Canada and Turkey an article in the New England Journal of Medicine entitled "Mutations in CYP24A1 and Idiopathic Infantile Hypercalcemia".

Vitamin D supplementation for the prevention of rickets is one of the oldest and most effective prophylactic measures in medicine, having virtually eradicated rickets in North America. Given the potentially toxic effects of vitamin D, the recommendations for the optimal dose are still debated, in part owing to the increased incidence of idiopathic infantile hypercalcemia in Britain in the 1950s during a period of high vitamin D supplementation in fortified milk products.

We elucidated the molecular basis of idiopathic infantile hypercalcemia, which is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recessive mutations in the vitamin D-metabolizing enzyme CYP24A1 were identified in six affected children. In addition, CYP24A1 mutations were identified in a second cohort of infants in whom severe hypercalcemia had developed after bolus prophylaxis with vitamin D.

Functional characterization revealed a complete loss of function in all CYP24A1 mutations. The presence of CYP24A1 mutations explains the increased sensitivity to vitamin D in patients with idiopathic infantile hypercalcemia and is a genetic risk factor for the development of symptomatic hypercalcemia that may be triggered by vitamin D prophylaxis in otherwise apparently healthy infants.

Article in The New England Journal of Medicine

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