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-dihydroxyvita-min 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 µg and 6 × 10⁶ 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.

Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets

“…12,68 Oral calcium alone has sometimes been successfully used as a therapy for HVDRR patients from the outset. [10][11][12]69 In one study calcium delivered via the enteral route using a gastric tube was successful in reversing the metabolic abnormalities in a case of HVDRR when maintaining an IV became problematic in a young child due to repeated infections of the intravenous line. 70 A recent study has suggested the use of Cinacalcet as an adjunctive therapy for treatment of the secondary hyperparathyroidism in HVDRR.…”

Genetic Disorders and Defects in Vitamin D Action

“…Once the child is older, perhaps when the skeleton has finished major growth, oral calcium often suffices to maintain normocalcemia and the IV calcium regimen can be discontinued [28]. Oral calcium alone has sometimes been successfully used as a therapy for HVDRR patients [57]. Spontaneous healing of rickets has been observed in some HVDRR patients as they get older and all therapy sometimes can be discontinued [11,26,27].…”

Vitamin D - Dependent Rickets, Type II Case Report

“…Slow disappearance of radiological changes in bones in line with normalization of other laboratory findings is in favour of diagnosis of vitamin D –dependent rickets type II. The other authors (11, 12) stated that the changes in bones were not that much visible in cases with this form of rickets (because the cases were diagnosed earlier) and these changes starter to disappear faster (after the second month) after use of the corresponding therapy.…”