Vitamin D-dependent rickets type 2B (VDDR2B)

(OMIM phenotype number #600785)

Vitamin D-dependent rickets type 2B (VDDR2B) is an unusual form of Vitamin D-dependent rickets due to abnormal expression of a hormone response element binding protein that interferes with the normal function of the VDR, without mutations in the VDR coding region. Hormone resistance resultes from constitutive overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) that competed with a normally functioning VDR-retinoid X receptor (RXR) dimer for binding to the vitamin D response element (VDRE). See also VDDR2A.

Phenotype

Growth retardation, muscle weakness, convulsion for hypocalcemia, bone pain at the lower extremities that delays their development of walking, dental caries or hypoplasia of the teeth, scalp and total alopecia, mild deafness, congenital rickets with fracture and pseudofractures, sparse bone trabeculae, thin bony cortex, delayed opacification of the epiphyses, widened, distorted epiphyses, frayed, irregular metaphyses, lower limb deformities, bowing of the legs, curvatures of the femur, tibia, fibula, enlargement of the wrists, enlargement of the ankles, and subperiosteal erosions due to secondary hyperparathyroidism.

Main biochemical alterations

High 1,25(OH)2D,  markedly high bone ALP, low Ca and high or normal PTH.

References

  1. Chen H, Hewison M, Adams JS. Functional characterization of heterogeneous nuclear ribonuclear protein C1/C2 in vitamin D resistance: a novel response element-binding protein. J Biol Chem. 2006 Dec 22;281(51):39114-20.
  2. Chen H, Hewison M, Hu B, et al. Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: a cause of vitamin D resistance. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6109-14.
  3. Hewison M, Rut AR, Kristjansson K, Walker RE, et al. Tissue resistance to 1,25-dihydroxyvitamin D without a mutation of the vitamin D receptor gene. Clin Endocrinol (Oxf). 1993 Dec;39(6):663-70.
  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