CYP24A1 Mutation in a Girl Infant with Idiopathic Infantile Hypercalcemia

CONTEXT: Idiopathic Infantile Hypercalcemia (IHH) was associated with vitamin-D supplementation in the 1950's. 50 years later mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology.

CASE DESCRIPTION: We hereby report a case of a 21 months old girl initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia, borderline high vitamin-D levels, and renal ultrasound revealed medullary nephrocalcinosis. An abnormality within the vitamin-D metabolism was suspected and genetic testing was performed. This revealed the patient to be compound heterozygous for a common (p.E143del) and a novel (likely) disease-causing mutation (p.H83D) in the CYP24A1 gene. The hypercalcemia normalized after calcium depleted diet and discontinuation of vitamin-D supplementation.

CONCLUSIONS: Increased awareness of the typical symptoms of hypercalcemia, such as anorexia, polydipsia, regurgitation and failure to thrive, is of utmost importance to diagnose IHH and prevent long term complications such as nephrocalcinosis. Further identification of as many disease-causing mutations in the CYP24A1 gene as possible can help identification of predisposed individuals where vitamin-D supplementation can be reconsidered.