Differential Diagnosis of Megaloblastic Anemia, due to Cobalamin Deficiency
• Usurping of luminal Cbl (inadequate Cbl binding to IF) • Nutritional Cbl deficiency (insufficient Cbl intake): vegetarians, vegans, breast-fed infants of mothers with pernicious anemia • Metabolic disorders (Cbl not used by cell) • Loss or atrophy of gastric oxyntic mucosa (deficient intrinsic factor [IF] molecules): total or partial gastrectomy, pernicious anemia, caustic destruction (lye) • Insufficiency of pancreatic protease: pancreatic insufficiency • Inborn enzyme errors (rare) • Inactivation of pancreatic protease: Zollinger-Ellison syndrome • IF/post IF receptor defects: Imerslund-Graesbeck syndrome, transcobalamin (TC) II deficiency • Drug-induced effects (Slow-K, biguanides, cholestyramine, colchicine, neomycin, p-aminosalicylic acid [PAS]) • Disorders of plasma Cbl transport (TC II–Cbl not delivered to TC II receptors) • Disorders of ileal mucosa/IF receptors (IF-Cbl not bound to IF receptors) • Diminished or absent IF receptors: ileal bypass, resection, or fistula • Congenital TC II deficiency, defective binding of TC II–Cbl to TC II receptors (rare) • By Diphyllobothrium latum • By bacteria; stasis syndromes (blind loops, pouches of diverticulosis, strictures, fistulas, anastomoses); impaired bowel motility (scleroderma, pseudo-obstruction); hypogammaglobulinemia • Acquired disorders: N2O inhalation • Abnormal mucosal architecture/function: tropical or Non tropical sprue, Crohn’s disease, TB ileitis, infiltration by lymphomas, amyloidosis • Abnormal intragastric events (inadequate proteolysis of food Cbl): atrophic gastritis, partial gastrectomy with hypochlorhydria • Abnormal events in small bowel lumen: inadequate pancreatic protease (R-Cbl not degraded, Cbl not transferred to IF)
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