Hereditary vitamin D-resistant rickets

Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest 1997 99[2] 297-304. 

W24 Williams, T. F., and Winters, R. W., Familial (hereditary) vitamin D resistant rickets with hypophosphatemia In The Metabolic Basis of Inherited Diseases (J. B. Stanbury, J. B. Wyngaarden, and D. S. Frederickson, eds.), 3rd Ed. McGraw-Hill, New York, 1972. 

S.A. Gardezi, C. Nguyen, P.J. Malloy, G.H. Posner, D. Feldman, S. Peleg, A rationale for treatment of hereditary vitamin D-resistant rickets with analogs of 1 alpha,25-dihydroxyvitamin D-3, J. Biol. Chem. 2001, 276, 29148-29156. 

Several disorders of tubular phosphate handhng have been described. The best known of these is X-linked dominant hypophosphatemic rickets (previously known as vitamin D-resistant rickets). This disorder arises because of a defect in the PHEX gene. A defect of the sodium-dependent/ phosphate co-transporter has also been described, giving rise to autosomal recessive hereditary hypophosphatemic rickets with hypercalciuria. The molecular biology of tliese and other renal phosphate transport disorders has been reviewed. ... 

An autosomal recessive disease known as hereditary vitamin D-resistant riekets, type II is caused by defects in the gene for the vitamin D receptor which renders it nonfunctional. Thus, this knockout of VDR function illustrates its importance. Patients with this disease have high circulating levels of 1,25-(OH)2D (unlike type 1 disease which is due to la-hydroxylase deficiency, discussed earlier), severe rickets, and alopecia. The alopecia may... 

Malloy PJ, Pike JW, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets. EndocrRev 1999 20(2) ... 

Conditions associated with abnormalities in calcitriol synthesis or response can cause rickets in children and osteomalacia in adults. Specific disorders include X-linked hypophosphatemic rickets due to mutations in the PHEX endoprotease, Vitamin D-dependent rickets due to mutations in la-hydroxylase, and hereditary l,25-(OH)J) resistance due to mutations in the VDR. 

Figure 1 This is a typical presentation of a child with rickets. The child is suffering from severe muscle weakness, has bony deformities including bowed legs, and knob-like projects in the middle of his ribcage called the rachitic rosary. (Reproduced with permission from Fraser D and Scriver CR (1979) Disorders associated with hereditary or acquired abnormalities of vitamin D function hereditary disorders associated with vitamin D resistance or defective phosphate metabolism. In De Groot LJ et al. (eds.) Endocrinology, pp. 797-808. New York Grune and Stratton.)...

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