title: Absent intestinal response to calciferols in hereditary resistance to 1,25-dihydroxyvitamin D: documentation and effective therapy with high dose intravenous calcium infusions.
abstract: We describe a patient with an absent intestinal response to 1,25-dihydroxyvitamin D [1,25-(OH)2D] and the beneficial effects of treatment with high dose iv calcium infusion. The patient presented with severe rickets despite therapy with extraordinarily high doses of 1 alpha-hydroxyvitamin D3 or 1,25-(OH)2D3. Unidirectional intestinal fractional calcium absorption when he was not treated with any calciferol was 14% (normal, 20-70%), as measured with stable calcium isotopes; no increase in calcium absorption occurred when serum 1,25-(OH)2D levels were more than 50-fold elevated. Cultured skin fibroblasts contained no detectable 25-hydroxyvitamin D3-24-hydroxylase activity in response to 1,25-(OH)2D3 (10(-9)-10(-6) mol/L). High dose iv calcium infusions and oral phosphorus supplementation for 135 days improved or normalized biochemical parameters and resulted in radiographic healing of the rachitic lesions. We conclude that 1) this patient had no response to 1,25-(OH)2D3 in vivo and in vitro; 2) long term parenteral calcium infusions were effective therapy in managing the patient's severe resistance to 1,25-(OH)2D; and 3) stable calcium isotopes are useful for measuring low levels of fractional calcium absorption.
authors.affiliation: Section on Mineral Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
authors.forename: M
authors.initials: M
authors.lastname: Bliziotes
authors.forename: A L
authors.initials: AL
authors.lastname: Yergey
authors.forename: M S
authors.initials: MS
authors.lastname: Nanes
authors.forename: J
authors.initials: J
authors.lastname: Muenzer
authors.forename: M G
authors.initials: MG
authors.lastname: Begley
authors.forename: N E
authors.initials: NE
authors.lastname: Vieira
authors.forename: K K
authors.initials: KK
authors.lastname: Kher
authors.forename: M L
authors.initials: ML
authors.lastname: Brandi
authors.forename: S J
authors.initials: SJ
authors.lastname: Marx
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002675:Child, Preschool; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000188:drug therapy* / Q000235:genetics; D007408:Intestinal Absorption; D008297:Male; D010758:Phosphorus / Q000008:administration & dosage / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects
chemical_list: D010758:Phosphorus; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium