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Diagnosis and Effect of Folate and Vitamin B12 Deficiency Leigh Ann Martin Advisor: Gilbert A. Boissonneault, PhD, PA-C, CN Background Vitamins Organic compounds that act as metabolic catalysts Two groups fat-soluble and water-soluble Focus of today’s presentation: folate and vitamin B12 Water-soluble vitamins important in the formation of red blood cells, the nervous system, and DNA Pathophysiology Folic acid and vitamin B12 Required for DNA synthesis and red cell maturation Two vitamins combine in methionine synthase reaction Methyl group is transferred to homocysteine to make methionine Decrease in either leads to increase in homocysteine level Premature Coronary Artery Disease Peripheral Vascular Disease Pathophysiology Deficiency leads to change in RBC shape Megaloblastic anemia is a subgroup of macrocytic anemias Megaloblastic erythropoiesis when defect in DNA synthesis and the cells are arrested at the G2 phase Becomes a buildup of cells that do not synthesize DNA so nucleus develops at a slower rate than the rest of the cell Cytoplasm continues to grow due to RNA synthesis Cells become larger and megalblastic Effects on the Body---Folate Main manifestations Lab work an increase in MCV-- larger than 96 fL Best test for folate levels is the red blood cell level glossitis, symptoms of anemia (weakness, pallor, shortness of breath), and GI problems (weight loss and infertility) this is the level in tissues and is not affected by recent intake Recommended intake of folate for adults is 400 micrograms per day, and for women of childbearing age is 600 micrograms per day Effects on the Body—vitamin B12 Main manifestations Lab work same as those for folate but may be a more serious presentation with peripheral neuropathy, degeneration of the spinal cord, or demyelination of white matter of brain Patient may present with difficulty walking, parasthesia, loss of memory function, and a positive Romberg test also shows an increase in size of MCV Recommended intake of vitamin B12 for adults is 2.4 micrograms per day, and for women of childbearing age is 2.6 micrograms per day Anticonvulsant drugs and folate deficiency Recent Drug Study Epileptic patients split into control and experimental group Experimental group using Phenytoin, Carbamazepine, and Valproic Acid Patients taking the antiepileptic medications had increased homocysteine levels and decreased red blood cell levels of folate Different Drugs No difference in level of homocysteine between all drugs Phenytoin shown to have lowest folic acid level Hyperhomocysteinemia Folate deficiency is number one cause Hyperhomocysteinemia is less than 12 micromoles per liter Closely related to CVD American Heart Association reported that 47% of all patients with CVD had hyperhomocysteinemia Treatment Distinguishing between the two vitamin deficiencies Treatment is to supply the vitamin Conclusion Both deficiencies present very much alike Important to distinguish between the two Monitor patients on anticonvulsants References Wickramsinghe SN. Diagnosis of megaloblastic anemias. Blood Reviews. 2006; 20 (6), 299-318 Porth C. Essentials of Pathophysiology: concepts of altered health status. Second Edition. Lippincott Williams and Wilkins. 2004; 168-169. Dale DA, Federman DA, Antman KA, Atkinson JO, Cassel CH, Feldman MA et al. ACP Medicine. Volume 1. 2006 Edition. New York: WebMD Inc; 2006. Carmel RA. Laboratory Diagnosis of Megaloblastic Anemia. Medical Progress. 1978 April;128(4):294-304. Sener UF, Zorlu YA, Karguzel OG, Ozdamar OZ, Coker IS, et al. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, Vitamin B12, folic acid and Vitamin B6. Seizure. 2006 Aug 24; 15: 79-85. Sadeghian SA, Fallahi FA, Salarifar MO, Davoodi GH, Mahmoodian ME, Fallah NA, et al. Homocysteine, vitamin B12 and folate levels in premature artery disese. BMC Cardiovascular Disorders. 2006 Sept 26; 6: 38.