An unique form of osteomalacia associated with end organ refractoriness to 1,25-dihydroxyvitamin D and apparent defective synthesis of 25-hydroxyvitamin D

A 28-yr-old woman presented with hypocalcemia, hypophosphatemia, secondary hyperparthyroidism, and biopsyproven osteomalacia despite treatment with vitamin D₂, (17.5 mg/day). Three weeks after vitamin D₂ treatment was stopped, she was found to have a low normal serum 25-hydroxyvitamin D (25OHD) and high serum 1α,25-dihydroxyvitamin D [1,25(OH)₂D] of 18.6 ng/ml and 21.2 ng/dl, respectively. The fractional intestinal calcium absorption was low at 0.26. Treatment with 25OHD₃ (20-50 μg/day) corrected the hypocalcemia and secondary hyperparathyroidism, raised intestinal calcium absorption, and reversed the skeletal lesions of osteomalacia. Serum 25OHD concentration rose to 51 ng/ml, while 1,25(OH)₂D remained elevated. This case illustrates the probable operation of dual abnormalities in vitamin D metabolism. An impaired end organ responsiveness to 1,25(OH)₂D was suggested by a low intestinal calcium absorption in the face of high serum 1,25(OH)₂D. Moreover, there may have been a defective vitamin D-25-hydroxylase, since there was a relative refractoriness to treatment with large doses of vitamin D₂, an inappropriately low serum 25OHD after vitamin D₂ therapy, and a responsiveness to treatment with 25OHD₃.