title: Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case reports and review of the literature.
abstract: Concurrent hemolysis in patients with vitamin B12 deficiency is a well-recognized phenomenon and has been attributed to intramedullary destruction of erythrocytes (ineffective erythropoiesis). Recent studies revealed that homocysteine increased the risk of hemolysis in vitamin B12 deficiency in vitro and there is a high frequency (30%) of vitamin B12 deficiency in asymptomatic patients with homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation, a known cause of hyperhomocysteinemia. Here we report three patients with MTHFR mutations and vitamin B12 deficiency presenting with hemolytic anemia and severely elevated homocysteine levels. Patients demonstrated complete resolution of hemolysis with simultaneous normalization of serum homocysteine levels after vitamin B12 treatments. We reviewed pertinent literature, and hypothesized that hemolytic anemia may be more prevalent in patients who have a coexisting MTHFR gene mutation and vitamin B12 deficiency possibly related to severely elevated homocysteine levels. The hemolysis in these cases occurred predominantly in peripheral blood likely due to the combined effects of structurally defective erythrocytes and homocysteine-induced endothelial damage with microangiopathy.
authors.affiliation: Department of Geriatric Medicine, Ohio University College of Osteopathic Medicine, Athens, OH, USA. utkarsh.h.acharya.1@ohio.edu
authors.forename: Utkarsh
authors.initials: U
authors.lastname: Acharya
authors.forename: Jen-Tzer
authors.initials: JT
authors.lastname: Gau
authors.forename: William
authors.initials: W
authors.lastname: Horvath
authors.forename: Paolo
authors.initials: P
authors.lastname: Ventura
authors.forename: Chung-Tsen
authors.initials: CT
authors.lastname: Hsueh
authors.forename: Wayne
authors.initials: W
authors.lastname: Carlsen
mesh_terms: D000369:Aged, 80 and over; D000743:Anemia, Hemolytic / Q000209:etiology*; D017707:Erythrocyte Transfusion; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D014805:Vitamin B 12 / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000235:genetics / Q000628:therapy
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12