Pernicious anemia, a megaloblastic anemia caused by B12 deficiency, is associated with hyperhomocysteinemia. Because B12 is needed for methionine synthase to methylate homocysteine to methionine, a deficiency causes an accumulation of both homocysteine and methylmalonic acid (1). When both are elevated, marking the pernicious anemia, it can lead to progressive demyelination and neurological deterioration.
A folate deficiency may also result in megaloblastic anemia. If homocysteine is elevated but not methylmalonic acid, then the result is probably a folate deficiency. It is important for treatment to be correct. Large doses of folate can correct, or “mask,” symptoms of pernicious anemia, which can result in irreversible neuropathy (2).
1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002
2. Pagana, K.D., Pagana, T.J. Mostby’s Manual of Diagnostic and Laboratory Tests, 3rd ed. Mosby Elsvier, 2006