Severely Deficient Binding of 1,25-Dihydroxyvitamin D to Its Receptors in a Patient Responsive to High Doses of This Hormone*

Abstract

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 fig, 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.