Juvenile onset IIH and <i>CYP24A1</i> mutations.

Schlingmann, Karl P; Cassar, Walburga; Konrad, Martin · Bone Rep · 2018

case_report · Level V

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Abstract

The term Idiopathic infantile hypercalcemia (IIH) was first introduced almost 70 years ago when symptomatic hypercalcemia developed in children after receiving high doses of vitamin D for the prevention of rickets. The underlying pathophysiology remained unknown until recessive mutations in <i>CYP24A1</i> encoding Vitamin D<sub>3</sub>-24-hydroxylase were discovered. The defect in vitamin D degradation leads to an accumulation of active 1,25(OH)<sub>2</sub>D<sub>3</sub> with subsequent hypercalcemia. Enhanced renal calcium excretions lead to hypercalciuria and nephrocalcinosis. Meanwhile, the phenotypic spectrum associated with <i>CYP24A1</i> mutations has significantly broadened. Patients may present at all age groups with symptoms originating from increased serum calcium levels as well as from increased urinary calcium excretions, i.e. kidney stones. Possible long term sequelae comprise chronic renal failure as well as cardiovascular disease. Here, we present a family with two affected siblings with differing clinical presentation as an example for the phenotypic variability of CYP24A1 defects.