Novel Mutation in CYP2R1 Causing Vitamin D-Dependent Rickets Type 1b

• Published in: JCEM case reports 2024, Vol.2 (3), p.luae024-luae024
• Main Authors: Menon, Jayakrishnan C, Kumari, Archana, Sajjan, Shruti M, Dabadghao, Preeti
• Format: Report
• Language: English
• ISSN: 2755-1520
• DOI: 10.1210/jcemcr/luae024

Monogenic forms of rickets are being increasingly recognized. However, vitamin D-dependent rickets 1b (VDDR1b) due to CYP2R1 gene mutation is exceedingly rare. We report a 4.5-year-old girl and her younger sibling who presented with clinical, radiological, and biochemical features suggestive of nutritional rickets that did not resolve despite repeated therapeutic doses of vitamin D3. This led to evaluation for resistant rickets, which revealed a novel homozygous CYP2R1 c.50_51insTCGGCGGCGC; p.Leu18ArgfsTer79 variant in the affected siblings. The children were treated with oral calcium and cholecalciferol, dose titrated to maintain serum alkaline phosphatase, 25 hydroxy vitamin D, and parathyroid hormone levels in the normal range, with good clinical and radiological response. This case highlights the importance of genetic evaluation in patients with suspected nutritional rickets who have a family history of similar illness and require higher than usual doses of vitamin D for healing or relapse on stopping treatment. To the best of our knowledge this is the first case of VDDR1b reported from Asia.