Severely deficient binding of 1,25-dihydroxyvitamin D to its receptors in a patient responsive to high doses of this hormone.
A 1.6-yr-old Hispanic boy with sparse hair, muscle weakness, severe growth retardation, and rickets was found to have hypocalcemia, secondary hyperparathyroidism, and high circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. One year of treatment with a high dose of 1,25-(OH)2D3 (20 micrograms, orally, daily) resulted in marked subjective and radiological improvement; there was a parallel improvement in serum calcium, phosphorus, PTH, alkaline phosphatase, and osteocalcin concentrations. Soluble extracts from cultured skin fibroblasts did not bind [3H]1,25-(OH)2D3 using standard methods. To evaluate the possibility of receptors with abnormally low affinity, we tested for binding with [3H]1,25-(OH)2D3 concentrations higher than those usually used. In one experiment, there was a suggestion of low affinity binding. Hormone receptors with abnormally low affinity for 1,25-(OH)2D may explain this patients resistance to 1,25-(OH)2D. Therapy to maintain extremely high serum 1,25-(OH)2D3 concentrations markedly improved mineral homoeostasis, but did not affect the hair disorder.
D002117:Calcitriol / Q000378:metabolism / Q000627:therapeutic use*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D007719:Knee Joint / Q000000981:diagnostic imaging; D008297:Male; D011859:Radiography; D011869:Radioligand Assay; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D012279:Rickets / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol