vitamin-d-2 and Metabolism--Inborn-Errors

A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject.

Topics: Bone Neoplasms; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Giant Cell Tumors; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Hypophosphatemia, Familial; Kidney Failure, Chronic; Metabolism, Inborn Errors; Nephrectomy; Osteomalacia; Phosphates; Pseudohypoparathyroidism; Vitamin D; Vitamin D Deficiency

Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated five patients (one male, four females) from four families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form, of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and posttreatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction, and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1,000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients.. Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects.

Topics: Acyltransferases; Adolescent; Bile Acids and Salts; Child; Child Development; Child, Preschool; Cholagogues and Choleretics; Ergocalciferols; Female; Glycocholic Acid; Humans; Infant; Male; Metabolism, Inborn Errors; Tocopherols

Topics: Adolescent; Adult; Alkaline Phosphatase; Deficiency Diseases; Ergocalciferols; Female; Humans; India; Male; Metabolism, Inborn Errors; Middle Aged; Osteomalacia; Pakistan; Radiography; Urban Population; Vitamin D