NOTE: Vitamin D resistant rickets (VDRR) is considered an inappropriate term since there is no resistance to vitamin D; however, the rickets does not respond to its administration.
Inheritance: X-linked dominant, complete penetrance with variable expression. Both men and women are affected even though a woman is heterozygous.
Genetic locus: Xp22.1
Affected molecule: phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX). The mutation interferes with degradation of FGF-23 (see previous section). This results in inhibition of renal tubular reabsorption of phosphate and reduced renal 1-alpha hydroxylase activity with reduced 1,25-dihydroxyvitamin D
Clinical findings:
(1) rickets in childhood and osteomalacia in the adult
(2) dental abnormalities (defective dentin, dental abscesses)
(3) minimal muscle weakness
(4) bone pain
(5) short stature with lower limb deformities (varus or valgus bowing)
(6) pathologic fractures
(7) enthesopathy (calcification of tendons, ligaments and joint capsules)
(8) cranial abnormalities with frontal bossing
Laboratory findings:
(1) hypophosphatemia
(2) normal serum and urine calcium levels
(3) low to normal serum 1,25-dihydroxyvitamin D
(4) serum parathyroid hormone level normal to elevated
(5) decreased renal threshold phosphate concentration (TmPO4/GFR)
(6) absence of glycosuria and aminoaciduria
(7) serum alkaline phosphatase increased
