Vitamin-D-Dependent Rickets Type II: Resistance of Target Organs to 1,25-Dihydroxyvitamin D

Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D₃, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II. (N Engl J Med 298:996–999, 1978) VITAMIN-D-dependent rickets is characterized by clinical and biochemical features of rickets that occur despite an adequate intake of vitamin D and can be entirely reversed by pharmacologic doses of vitamin D.^{1 2 3} Recent evidence suggests that the basic abnormality is diminished renal synthesis of 1,25-dihydroxyvitamin D.^{1 2 3} Thus, patients with this disease have been shown to respond to small doses of 1,25-dihydroxyvitamin D₃^1,2 or 1,α-hydroxyvitamin D₃,³ and in one case, serum 1,25-dihydroxyvitamin D was found to be below the limits of detection by a binding assay.⁴ The patient with osteomalacia described below had hypocalcemia and secondary hyperparathyroidism in association.