Hereditary resistance to 1,25-dihydroxyvitamin D: clinical and radiological improvement during high-dose oral calcium therapy

Abstract

A 6-year-old boy, of consanguinous parents, presented with severe rickets and alopecia; he was found to have hypocalcaemia and elevated circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. He showed no calcaemic response to 1,25-(OH)2D3 or ergocalciferol given for 3 or more months in daily doses as high as 48 micrograms and 6 X 10(6) IU, respectively. Analyses with cultured skin fibroblasts revealed a normal capacity and affinity for 1,25-(OH)2D3 in soluble extracts ('cytosol') and in nuclei of intact cells but no detectable response of 25-(OH)D3 24-hydroxylase to 1,25-(OH)2D3 in high concentration. Treatment with high doses of calcium (3-4 g elemental calcium orally per day) produced a striking clinical and radiological improvement. We conclude that high oral doses of calcium can replace many of the actions of calciferols. Therapy with high doses of calcium should be tried in similarly affected cases that appear totally or partially unresponsive to calciferols.