​Differential Diagnosis of Megaloblastic Anemia, due to Cobalamin Deficiency

​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)