Background: Homozygous or compound heterozygous mutations of gene CYP24A1 have recently been reported to cause idiopathic infantile hypercalcemia due to increased intestinal absorption of calcium. However, an autosomal dominant transmission with partial penetrance of the trait was also suggested.
Objective and hypotheses: Evaluation of the frequency of CYP24A1 mutation and evaluation of the impact of heterozygous mutation on calcium metabolism.
Methods: We screen for CYP24A1 mutation in a cohort of 90 probands presenting with hypercalcemia (>2.6 mmol/l) and low PTH levels (<20 pg/ml) and 35 relatives. Biochemical data were obtained with routine methods. Calcium absorption studies were performed in eight family members using PAK test that consists in the evaluation of calciuria after oral calcium administration. Serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were assessed by liquid chromatography tandem mass spectrometry (LCMSMS).
Results: Bi-allelic mutations were found in 21 patients (23%) and seven patients were heterozygous (7%). Fifteen mutations have never been described. In eight asymptomatic relatives carrying heterozygous CYP24A1 mutations, we observed normal P/Ca/PTH level. However, five patients had high 1,25-(OH)2D level. Digestive absorption of calcium was at the upper limits of normal in three patients. Blood samples were tested with LCMSMS in 14 patients without mutations, 17 with heterozygous mutation and three with bi-allelic mutations. Low 24,25-dihydroxyvitamin D level and high ratio of 25-hydroxyvitamin D: 24,25-dihydroxyvitamin D (M=102) were found in 3/3 patients with bi allelic mutation. There is no difference between patients carrying heterozygous mutation (M=14.3) and patients with hypercalcemia without CYP24A1 mutations (M=19.8), but heterozygous carriers exhibit higher 25-hydroxyvitamin D levels than subjects without mutation.
Conclusion: Taken together, these elements do not suggest an increased risk of hypercalcemia for heterozygous patients, but seem to indicate a protective factor for vitamin D deficiency.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology