megaloblastic anemia


Summary: A disorder characterized by the presence of ANEMIA, abnormally large red blood cells (megalocytes or macrocytes), and MEGALOBLASTS.

Top Publications

  1. Khanduri U, Sharma A. Megaloblastic anaemia: prevalence and causative factors. Natl Med J India. 2007;20:172-5 pubmed
    ..Physicians managing these patients need to be aware of the timing of blood sampling for assays, that haematinics and transfusions provide only short term benefits, and that long term follow up and diet counselling is crucial. ..
  2. Wickramasinghe S. Diagnosis of megaloblastic anaemias. Blood Rev. 2006;20:299-318 pubmed
    ..At least 25% of low serum B(12) levels are not associated with elevated metabolite levels and may not indicate B(12) deficiency. Some of these are caused by partial deficiency of transcobalamine I. ..
  3. Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, et al. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region. Blood. 1998;91:3593-600 pubmed
    ..This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by ..
  4. Neufeld E, Mandel H, Raz T, Szargel R, Yandava C, Stagg A, et al. Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. Am J Hum Genet. 1997;61:1335-41 pubmed
    Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and ..
  5. Aminoff M, Carter J, Chadwick R, Johnson C, Gräsbeck R, Abdelaal M, et al. Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat Genet. 1999;21:309-13 pubmed
    ..Our genetic and molecular data indicate that mutations in CUBN cause MGA1. ..
  6. Fleming J, Tartaglini E, Steinkamp M, Schorderet D, Cohen N, Neufeld E. The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Nat Genet. 1999;22:305-8 pubmed
    ..3 critical region. Here we present evidence that the gene SLC19A2 (for solute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transporter-1 (THTR-1). ..
  7. Kristiansen M, Aminoff M, Jacobsen C, de la Chapelle A, Krahe R, Verroust P, et al. Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. Blood. 2000;96:405-9 pubmed
    b>Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the selective intestinal malabsorption of intrinsic factor (IF) and vitamin B(12)/cobalamin (Cbl) in complex...
  8. Rindi G, Casirola D, Poggi V, De Vizia B, Patrini C, Laforenza U. Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia. J Inherit Metab Dis. 1992;15:231-42 pubmed
  9. He Q, Fyfe J, Schäffer A, Kilkenney A, Werner P, Kirkness E, et al. Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome. 2003;14:758-64 pubmed
    ..of cobalamin (vitamin B(12)) accompanied by proteinuria, known as Imerslund-Gräsbeck syndrome or megaloblastic anemia 1 (I-GS, MGA1; OMIM 261100), is a rare autosomal recessive disorder...

More Information


  1. Gräsbeck R. Megaloblastic Anaemia (MA). Hematology. 2005;10 Suppl 1:227-8 pubmed
  2. Diaz G, Banikazemi M, Oishi K, Desnick R, Gelb B. Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. Nat Genet. 1999;22:309-12 pubmed
    ..The sequence homology and predicted structure of SLC19A2, as well as its role in TRMA, suggest that its gene product is a thiamine carrier, the first to be identified in complex eukaryotes. ..
  3. Tanner S, Aminoff M, Wright F, Liyanarachchi S, Kuronen M, Saarinen A, et al. Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nat Genet. 2003;33:426-9 pubmed
    ..exons 1-4 of human AMN lead to selective malabsorption of vitamin B12 (a phenotype associated with megaloblastic anemia 1, MGA1; OMIM 261100; refs...
  4. Aslinia F, Mazza J, Yale S. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res. 2006;4:236-41 pubmed
  5. Chen M, Logan T, Hochberg M, Shelat S, Yu X, Wilding G, et al. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction. Blood. 2009;114:4045-53 pubmed publisher
    ..These abnormalities are phenotypically similar to those found in patients with refractory anemia, suggesting that, in some cases, the myelodysplastic syndromes are caused by abnormalities of mitochondrial function. ..
  6. Lagarde W, Underwood L, Moats Staats B, Calikoglu A. Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. Am J Med Genet A. 2004;125A:299-305 pubmed
    Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine-responsive anemia...
  7. Tanner S, Li Z, Bisson R, Acar C, Oner C, Oner R, et al. Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East. Hum Mutat. 2004;23:327-33 pubmed
    Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the ..
  8. Koury M, Price J, Hicks G. Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism. Blood. 2000;96:3249-55 pubmed
    Deficiency of folate or vitamin B(12) (cobalamin) causes megaloblastic anemia, a disease characterized by pancytopenia due to the excessive apoptosis of hematopoietic progenitor cells...
  9. Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, et al. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat Genet. 1999;22:300-4 pubmed
  10. Ruiz Arguelles G, Lopéz Martínez B, Ruiz Reyes G. Heterozygous beta-thalassemia: not infrequent in Mexico. Arch Med Res. 2001;32:293-5 pubmed
    ..5 times more frequent than beta-thalassemia and that the latter is 1.3 times more frequent than macrocytic/megaloblastic anemia. beta-thalassemia should not be considered as infrequent in Mexico, and individuals with red blood cell ..
  11. Arora K, Sequeira J, Hernandez A, Alarcon J, Quadros E. Behavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse. PLoS ONE. 2017;12:e0177156 pubmed publisher
    Vitamin B12 (cobalamin) deficiency is prevalent worldwide and causes megaloblastic anemia and neurologic deficits. While the anemia can be treated, the neurologic deficits can become refractive to treatment as the disease progresses...
  12. Ayala E, Frisancho O, Yupanqui P. [Histological changes of the distal ileum in chronic diarrhea associated with megaloblastic anaemia]. Rev Gastroenterol Peru. 2004;24:117-21 pubmed
    ..The quick response to cobalamins and folates treatment showed the important role of these elements in intestinal restoration. ..
  13. Segbena A, Ambofo Planche Y, Gbadoe A, Dogba A, Kueviakoe I, Vovor A, et al. [Four case reports of Biermer's anemia in West Africa]. Med Trop (Mars). 2003;63:593-6 pubmed
    ..The authors recommend iron deficiency testing during the course of the disease and gastric biopsy during fibroscopy of upper digestive tract even if no macroscopic lesions are found. ..
  14. Sinha M, Panigrahi I, Shukla J, Khanna A, Saxena R. Spectrum of anemia in pregnant Indian women and importance of antenatal screening. Indian J Pathol Microbiol. 2006;49:373-5 pubmed
    ..3%) had dimorphic anemia, and 14 (11.6%) had hemolytic anemia. Megaloblastic anemia was present in 6 (5%). Of hemolytic anemia, 50% were thalassemia trait...
  15. Watermeyer S, Mukherjee S, Myers K, Parveen S, Asaad K. Severe megaloblastic anaemia compounding pre-eclampsia in a term pregnancy. J Obstet Gynaecol. 2004;24:928-9 pubmed
  16. Zariņa G, Sholts S, Tichinin A, Rudovica V, Viksna A, Engīzere A, et al. Cribra orbitalia as a potential indicator of childhood stress: Evidence from paleopathology, stable C, N, and O isotopes, and trace element concentrations in children from a 17th-18th century cemetery in J?kabpils, Latvia. J Trace Elem Med Biol. 2016;38:131-137 pubmed publisher
    ..g., megaloblastic anemia) and parasitism...
  17. Yadav M, Manoli N, Madhunapantula S. Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia. PLoS ONE. 2016;11:e0164559 pubmed publisher
    b>Megaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail ..
  18. Akinci A, Tezic T, Erturk G, Tarim O, Dalva K. Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness. Acta Paediatr Jpn. 1993;35:262-6 pubmed
    ..enzyme deficiency associated with diabetes mellitus, sensorineural deafness and thiamine-responsive megaloblastic anemia. Diabetes mellitus was diagnosed when she was 20 months old...
  19. Bender D. Megaloblastic anaemia in vitamin B12 deficiency. Br J Nutr. 2003;89:439-41 pubmed
  20. Yesilkaya E, Bideci A, Temizkan M, Kaya Z, Camurdan O, Koc A, et al. A novel mutation in the SLC19A2 gene in a Turkish female with thiamine-responsive megaloblastic anemia syndrome. J Trop Pediatr. 2009;55:265-7 pubmed publisher
    Reported here is a 2-year-old girl who was diagnosed to have thiamine-responsive megaloblastic anemia during evaluations for her bilateral neurosensorial deafness...
  21. Gabilondo A, Baeza I, Font E. Megaloblastic anemia and osteopenia in an adolescent diagnosed with schizophrenia. J Am Acad Child Adolesc Psychiatry. 2007;46:436-7 pubmed
  22. Bergmann A, Sahai I, Falcone J, Fleming J, Bagg A, Borgna Pignati C, et al. Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. J Pediatr. 2009;155:888-892.e1 pubmed publisher
    ..mutations and clinical status of 7 previously unreported kindreds with TRMA syndrome, (thiamine-responsive megaloblastic anemia, online Mendelian inheritance in man, no. 249270), a recessive disorder of thiamine transporter Slc19A2...
  23. Chandra J, Jain V, Narayan S, Sharma S, Singh V, Kapoor A, et al. Folate and cobalamin deficiency in megaloblastic anemia in children. Indian Pediatr. 2002;39:453-7 pubmed
  24. Saubade F, Hemery Y, Rochette I, Guyot J, Humblot C. Influence of fermentation and other processing steps on the folate content of a traditional African cereal-based fermented food. Int J Food Microbiol. 2018;266:79-86 pubmed publisher
    Folate deficiency can cause a number of diseases including neural tube defects and megaloblastic anemia, and still occurs in both developed and developing countries...
  25. Erkurt M, Aydogdu I, Bayraktar N, Kuku I, Kaya E. The levels of nitric oxide in megaloblastic anemia. Turk J Haematol. 2009;26:197-200 pubmed investigate the relationship between nitric oxide degradation products (nitrate and nitrite) levels and megaloblastic anemia which is treated with cyalocobalamin...
  26. Fadyl H, Inoue S. Combined B12 and iron deficiency in a child breast-fed by a vegetarian mother. J Pediatr Hematol Oncol. 2007;29:74 pubmed
  27. Schoueri Júnior R, de Carvalho Filho E, Curiati J, Lemos Neto C. [Megaloblastic anemia in the elderly]. Rev Paul Med. 1990;108:148-52 pubmed the Clinics Hospital of the School of Medicine of the University of São Paulo, who were admitted with megaloblastic anemia. Ages varied from 62 to 84 (mean 70.4 years)...
  28. Boros L, Steinkamp M, Fleming J, Lee W, Cascante M, Neufeld E. Defective RNA ribose synthesis in fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA). Blood. 2003;102:3556-61 pubmed
    Fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA) syndrome with diabetes and deafness undergo apoptotic cell death in the absence of supplemental thiamine in their cultures...
  29. Bennett M. Vitamin B12 deficiency, infertility and recurrent fetal loss. J Reprod Med. 2001;46:209-12 pubmed
    ..A more prolonged deficiency results in infertility by causing changes in ovulation or development of the ovum or changes leading to defective implantation. ..
  30. Al Alami J, Tanner S, Tayeh M, de la Chapelle A, El Shanti H. Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005;26:1061-4 pubmed
    Juvenile megaloblastic anemia is a rare and often hereditary disorder of cobalamin absorption, transport or intracellular metabolism...
  31. Dan K. [Drug-induced anemia]. Nihon Rinsho. 2008;66:540-3 pubmed
    ..Hemolytic anemias are included in the former and megaloblastic anemia, ringed sideroblastic anemia and pure red cell aplasia are included in the latter...
  32. Guerra Shinohara E, Morita O, Pagliusi R, Blaia d Avila V, Allen R, Stabler S. Elevated serum S-adenosylhomocysteine in cobalamin-deficient megaloblastic anemia. Metabolism. 2007;56:339-47 pubmed
    ..SAM), SAH, total homocysteine (tHcy), and methylmalonic acid (MMA) in 15 subjects with cobalamin-deficient megaloblastic anemia and compared results with those of 19 subjects with anemia/pancytopenia due to other causes...
  33. Chandra J, Jain V, Narayan S, Sharma S, Singh V, Batra S, et al. Tremors and thrombocytosis during treatment of megaloblastic anaemia. Ann Trop Paediatr. 2006;26:101-5 pubmed
    ..In one child, the platelet count increased to >1300 x 10(9)/L. The importance of recognising these clinical findings during treatment of megaloblastic anaemia is emphasised. ..
  34. Sullivan A. Prevalence and etiology of acquired anemia in Medieval York, England. Am J Phys Anthropol. 2005;128:252-72 pubmed
    ..chronic disease (ACD) caused by the body's natural iron-withholding defense against microbial invaders, and megaloblastic anemia caused by insufficient intake and/or absorption of vitamin B(12) or folic acid...
  35. Chandra J. Megaloblastic anemia: back in focus. Indian J Pediatr. 2010;77:795-9 pubmed publisher
    b>Megaloblastic anemia (MA), in most instances in developing countries, results from deficiency of vitamin B(12) or folic acid. Over the last two to three decades, incidence of MA seems to be increasing...
  36. Schiff M, Ogier de Baulny H, Bard G, Barlogis V, Hamel C, Moat S, et al. Should transcobalamin deficiency be treated aggressively?. J Inherit Metab Dis. 2010;33:223-9 pubmed publisher
    ..Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications...
  37. Ricketts C, Minton J, Samuel J, Ariyawansa I, Wales J, Lo I, et al. Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. Acta Paediatr. 2006;95:99-104 pubmed
    ..A mutation screening strategy is feasible and likely to identify mutations in almost all cases. ..
  38. Thameem F, Wolford J, Bogardus C, Prochazka M. Analysis of slc19a2, on 1q23.3 encoding a thiamine transporter as a candidate gene for type 2 diabetes mellitus in pima indians. Mol Genet Metab. 2001;72:360-3 pubmed
    Mutations in the SLC19A2 gene cause thiamine-responsive megaloblastic anemia (TRMA) frequently combined with diabetes mellitus and deafness...
  39. Heaney R. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr. 2003;78:912-9 pubmed
  40. van Amsterdam J, Nabben T, van den Brink W. Recreational nitrous oxide use: Prevalence and risks. Regul Toxicol Pharmacol. 2015;73:790-6 pubmed publisher
    ..and initially causing numbness in fingers, which may further progress to peripheral neuropathy and megaloblastic anemia. N2O use does not seem to result in dependence...
  41. Kuhn C, Kuhn A, Markau S, Kästner U, Osten B. Effect of immunoadsorption on refractory idiopathic focal and segmental glomerulosclerosis. J Clin Apher. 2006;21:266-70 pubmed
    ..Immunoadsorption was performed as a last resort to manage the nephrotic syndrome, which led to a drastic urinary protein reduction. We review the literature supporting immunoadsorption in primary focal segmental glomerulosclerosis. ..
  42. Gale D, Cobbold J, Chataway J. Steroid-responsive functional B12 deficiency in association with transcobalamin II polymorphism 776C --> G. Eur J Haematol. 2006;76:75-8 pubmed
    ..g. serum homocysteine) in excluding B12 deficiency, the role of steroids in pernicious anaemia and a possible clinical correlation of a TCII polymorphism. ..
  43. Sniekers M, Foulon V, Mannaerts G, Van Maldergem L, Mandel H, Gelb B, et al. Thiamine pyrophosphate: an essential cofactor for the alpha-oxidation in mammals--implications for thiamine deficiencies?. Cell Mol Life Sci. 2006;63:1553-63 pubmed
    ..considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA)...
  44. Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S. Thiamine responsive megaloblastic anemia syndrome. Indian J Pediatr. 2009;76:313-4 pubmed publisher
    Thiamine responsive megaloblastic anemia syndrome (TRMA) is a clinical triad characterized by thiamine-responsive anemia, diabetes mellitus and sensorineural deafness...
  45. Madhavan S, Vijayakumar M, Rajajee S, Nammalwar B. Imerslund-Grasbeck syndrome: association with diabetes mellitus. Indian Pediatr. 2009;46:251-3 pubmed
    ..During follow-up, he developed ketoacidosis due to insulin dependent diabetes mellitus. This rare combination has not been reported in the Indian literature. ..
  46. Hutin Y, Eugene C. [Tropical sprue revealed by severe anemia in a woman from Guadeloupe]. Gastroenterol Clin Biol. 1992;16:278-80 pubmed
    The case of a young woman from Guadeloupe developing severe megaloblastic anemia is reported. She presented with fever and hemolysis (she had heterozygotic beta-thalassemia) after a six month history of diarrhea...
  47. Stark G, Hamilton P. Dietary folate deficiency with normal red cell folate and circulating blasts. J Clin Pathol. 2003;56:313-5 pubmed
    ..We also highlight the need to recognise the non-linear relation between haematocrit and red blood cell folate concentration when the haematocrit is very low (< 0.15) and emphasise the importance of the clinical history. ..
  48. Lorber A, Gazit A, Khoury A, Schwartz Y, Mandel H. Cardiac manifestations in thiamine-responsive megaloblastic anemia syndrome. Pediatr Cardiol. 2003;24:476-81 pubmed
    Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine ..
  49. Czeczot H. [Folic acid in physiology and pathology]. Postepy Hig Med Dosw (Online). 2008;62:405-19 pubmed
    ..g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals. ..
  50. Ruiz Magaz M, Garrido Calvo S, Soler Gonzalez J, Jover Saenz A. [Pancytopaenia in a young black woman as a way that megaloblastic anaemia presents]. Aten Primaria. 2004;34:103-4 pubmed
  51. Vuylsteke P, Bertrand C, Verhoef G, Vandenberghe P. Case of megaloblastic anemia caused by intestinal taeniasis. Ann Hematol. 2004;83:487-8 pubmed
    A 61-year-old eutrophic male was diagnosed with vitamin B12 deficiency and megaloblastic anemia. A modified Schilling test suggested intestinal malabsorption unrelated to intrinsic factor deficiency...
  52. Nosaka K, Onozuka M, Kakazu N, Hibi S, Nishimura H, Nishino H, et al. Isolation and characterization of a human thiamine pyrophosphokinase cDNA. Biochim Biophys Acta. 2001;1517:293-7 pubmed
    ..The chromosome localization of the hTPK1 gene was assigned to 7q34. ..
  53. Shenoy V, Patil P, Nagar V, Deshpande A, Shedge R, Badiye A, et al. Congestive cardiac failure and anemia in a 15-year-old boy. J Postgrad Med. 2005;51:225-7 pubmed