Vitamin D hydroxylation-deficient rickets type 1B (VDDR1B)

(OMIM phenotype number #600081)

Vitamin D hydroxylation-deficient rickets type 1B (VDDR1B) is due to a defect in vitamin D 25-hydroxylation, and is caused by mutation in the CYP2R1 gene. The synthesis of bioactive vitamin D requires hydroxylation at the 1 α and 25 positions by cytochrome P450 enzymes in the kidney and liver, respectively. The mitochondrial enzyme CYP27B1 catalyzes 1 α-hydroxylation in the kidney, and the CYP2R1 is the major enzyme for hydroxylation of vitamin D to 25-hydroxyvitamin D. See also VDDR1A.

Gene

CYP2R1 gene, 11p15.2 (OMIM gene/locus number #608713).

Phenotype

Hypotonia, muscle weakness, difficulty in walking, difficulty in standing, congenital rickets with fractures, bone pain, sparse bone trabeculae, thin bony cortex, delayed opacification of the epiphyses, widened, distorted epiphyses, frayed, irregular metaphyses, lower limb deformities, and bowing of the legs.

Main biochemical alterations

Low Ca, low Pi, high bone ALP, normal 1,25(OH)2D, decreased 25 OH D.

References

  1. Thacher TD, Fischer PR, Singh RJ et al.  CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency. J Clin Endocrinol Metab. 2015 Jul;100(7):E1005-13.
  2. Casella SJ, Reiner BJ, Chen TC, et al.  A possible genetic defect in 25-hydroxylation as a cause of rickets. J Pediatr. 1994 Jun;124(6):929-32.
  3. Cheng JB, Levine MA, Bell NH, et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5.
  4. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  5. http://www.omim.org