25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations

• Main Authors: Sarah Bakhamis, Faiqa Imtiaz, Khushnooda Ramzan, Edward De Vol, Osamah Al-Sagheir, Abdulrahman Al-Rajhi, Abdullah Alashwal, Bassam Bin Abbas, Nadia Sakati, Afaf Al-Sagheir
• Format: Article
• Language: English
• Published: Bioscientifica 2021-07-01
• Series: Endocrine Connections
• Subjects: vitamin d; cyp2r1 mutation; 25-hydroxylase deficiency; rickets; saudi arabia
• Online Access: https://ec.bioscientifica.com/view/journals/ec/10/7/EC-21-0102.xml

Vitamin D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly, inheritance causes. Rece ntly, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency. We conducted a prospective cohort study at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, to review cas es with 25-hydroxylase deficiency and describe their clinical, biochemical, and molecul ar genetic features. We analyzed 27 patients from nine different families who presented with low 25-OH vitamin D and not responding to usual treatment. Genetic testing identi fied two mutations: c.367+1G>A (12/27 patients) and c.768dupT (15/27 patients), whe re 18 patients were homozygous for their identified mutation and 9 patients were het erozygous. Both groups had similar clinical manifestations ranging in severity, but no ne of the patients with the heterozygous mutation had hypocalcemic manifestations. Thirteen out of 18 homozygous patients and all the heterozygous patients responded to high doses of vitamin D treatment, but they regressed after decreasing the dose, requiring lifelon g therapy. Five out of 18 homozygous patients required calcitriol to improve their bioche mical data, whereas none of the heterozygous patients and patients who carried the c.367 +1G>A mutation required calcitriol treatment. To date, this is the largest cohort serie s analyzing CYP2R1-related 25-hydroxylase deficiency worldwide, supporting its major role i n 25-hydroxylation of vitamin D. It is suggested that a higher percentage of CYP2R1 mutations might be found in the Saudi population. We believe that our study will help in th e diagnosis, treatment, and prevention of similar cases in the future.