Does everyone need to take vitamin D? High prevalence of CYP24A1 deficiency in the Russian population

24-hydroxylase deficiency (or infantile hypercalcemia type 1) is an inherited disease associated with biallelic loss-of-function CYP24A1 mutations lead to impaired inactivation of vitamin D metabolites and characterised hypercalcemia, nephrocalcinosis and/or urolithiasis. We present 44 patients, the largest group (n=41) consisted of children. The main complaints at the time of examination was: weight loss, refusal to eat, delayed physical and/or psychomotor development, signs of urinary tract infection and/or nephrocalcinosis (in adults — urolithiasis). Hypercalcemia was detected in 88.6%, with Me 2.9 [2.65; 4.03] mmol/L. Me of the 25(OH)D3:24.25(OH)2D3 ratio was 340.65 [132.2; 630.75] (n=10). Hypercalciuria was detected in 59%, nephrocalcinosis or urolithiasis in 95% of cases. Frequent mutations in the CYP24A1 gene were p.Arg396Trp (66%) and p.Glu143del. (27%). Incidence of 24-hydroxylase deficiency in Russian population was 1:10900 estimated on the basis of these alleles of CYP24A1, overall carrier frequency for these mutations in CYP24A1 was 1 in 53 people. In conclusion, we propose to conduct molecular testing for the presence of pathogenic variants p.Arg396Trp and p.Glu143del in CYP24A1 during neonatal screening, due to the high expected frequency of 24-hydroxylase deficiency and heterozygous carriage of pathogenic variants of CYP24A1 in Russia.

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