Snapshot A 72-year-old man of European ancestry presents for a routine check-up with increased fatigue, a smooth shiney tongue and yellowing of his skin. The man is a strict vegan and refuses to eat anything that casts a shadow. On physical exam you note markedly decreased vibration sensation and proprioception. A peripheral smear is ordered demonstrating large RBC's as well neutrophils with nuclei that have 7 lobes. Introduction A megaloblastic anemia resulting from decreased DNA synthesis with normal RNA/protein synthesis Pernicious anemia is the most common cause of vitamin B12 deficiency antibody to gastric parietal cell leads to ineffective secretion of intrinsic factor (IF) leads to vitamin B12 deficiency due to decreased uptake in terminal ileum accompanied by achlorhydia and atrophic gastritis atrophic gastritis increases risk of gastric cancer must monitor periodically with fecal occult blood testing found mainly in mature persons of Northern European or African descent neuro findings caused by demyelination Other causes include malabsorption secondary to total or partial gastric resection loss of IF producing cells resection of terminal ileum drugs azathioprine zidovudine intestinal infections Diphyllobothrium latum Presentation Symptoms of megaloblastic anemia WITH neurological symptoms neurological findings numbness and parasthesias of the extremities (worse in legs) hyporeflexias decreased vibratory sensation ataxia demetia gastrointestinal findings glossitis Evaluation Best initial test: CBC and peripheral smear Most accurate test: B12 levels Serum B12 levels can be misleading at times Confirmatory tests ↑ serum methylmalonic acid ↑ homocysteine levels anti-intrinsic factor and parietal antibodies Schilling's test not relevant clinically (but on Step exams) Peripheral blood and marrow smear show hypersegmented neutrophils and megalocytes B12 and folate needed in DNA synthesis defect results in large immature nuclei in all nucleated cells pancytopenia most of these abnormal cells are destroyed Get TSH to rule out hypothyroidism Differential Macrocytic anemia alcoholism folate deficiency vitamin B12 deficiency hypothyroidism liver dysfunction drugs (methotrexate, phenytoin, trimethoprim, and zidovudine) Treatment Treat with monthly vitamin B12 injections high dose oral treatment proven to be equivalent in patients that can absorb B12