ESPE Abstracts

Background: Vitamin-D deficiency becomes a worldwide issue, and major cause of rickets in younger age groups. Multiple causes lead to vitamin-D deficiency in which nutritional causes contribute the major factor. The synthesis of bioactive vitamin-D requires hydroxylation at 1α and 25 positions by cytochrome-P450 in the kidney and liver, respectively. Recently, human CYP2R1 has been reported as a major factor for 25-hydroxylation, in which it contributes for the inherited forms of vitamin-D deficiency. Till now, five cases with CYP2R1 mutation were reported worldwide.

Method: A retrospective cohort study conducted in King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia. We included 36 patients who presented with classical symptoms of vitamin-D deficiency whom minimally responded to vitamin-D supplement. Their charts were reviewed for demographic, clinical, laboratory and radiological data. Genetic testing was sent for CYP2R1 mutation.

Results: Of 36 patients, 14 were homozygous affected, 19 were heterozygous carrier and three without detected mutation. Two different mutations were identified: c.367+1,G>A (25.7%) and c.768,insT (68.6%). The commonest presentation was bone pain (50%), followed by limitation of physical activity (33.3%) and short stature (27.8%). Some patients showed improvement with high doses of vitamin-D supplement, where others required the active form (1,25OH vitamin-D) for their treatment.

Conclusion: Our data identify that CYP2R1 plays a major role in 25-hydroxylation, which is a fundamental role in activation of vitamin-D. Higher percentage of CYP2R1 mutation related vitamin-D deficiency might find in our community. This result will help in diagnosing, treatment and prevention of similar cases in the future.