Blood Reviews
Volume 20, Issue 6 , Pages 299-318 , November 2006

Diagnosis of megaloblastic anaemias

References 

  1. Wickramasinghe SN, Rezvani K. The measurement of serum vitamin B12, serum folate and red cell folate. In:  Rowan RM,  van Assendelft OW,  Preston FE editor. Advanced Laboratory Methods in Haematology. London: Arnold; 2002;p. 264–289
  2. Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol. 1990;34:99–107
  3. Carmel R, Green R, Jacobsen DW, Rasmussen K, Florea M, Azen C. Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: Ethnic and sex differences in cobalamin and metabolite abnormalities. Am J Clin Nutr. 1999;70:904–910
  4. Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate, and homocysteine. Hematology (Am Soc Hematol Educ Program). 2003;62–81
  5. Carmel R. Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations. Clin Chem. 2003;49:1367–1374
  6. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med. 1994;96:239–246
  7. Allen RH, Stabler SP, Savage DG, Lindenbaum J. Diagnosis of cobalamin deficiency I: Usefulness of serum methylmalonic acid and total homocysteine concentrations. Amer J Hematol. 1990;4:90–98
  8. Wickramasinghe SN, Ratnayaka ID. Limited value of serum holo-transcobalamin II measurements in the differential diagnosis of macrocytosis. J Clin Pathol. 1996;49:755–758
  9. Miller JW, Garrod MG, Rockwood AL, Kushnir MM, Allen LH, Haan MN, et al. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem. 2005;Dec 29; Epub ahead of print
  10. Hvas AM, Nexo E. Holotranscobalamin as a predictor of vitamin B12 status. Clin Chem Lab Med. 2003;41:1489–1492
  11. Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. 2003;41:1478–1488
  12. Nilsson K, Isaksson A, Gustafson L, Hultberg B. Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms. Clin Chem Lab Med. 2004;42:637–643
  13. Herrmann W, Obeid R, Schorr H, Geisel J. The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Curr Drug Metab. 2005;6:47–53
  14. Chen X, Remacha AF, Sarda MP, Carmel R. Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II. Am J Clin Nutr. 2005;81:110–114
  15. Metz J, Kelly A, Swett VC, Waxman S, Herbert V. Deranged DNA synthesis by bone marrow from vitamin B-12-deficient humans. Br J Haematol. 1968;14:575–592
  16. Wickramasinghe SN. The deoxyuridine suppression test: a review of its clinical and research applications. Clin Lab Haematol. 1981;3:1–18
  17. Wickramasinghe SN, Matthews JH. Deoxyuridine suppression: biochemical basis and diagnostic applications. Blood Rev. 1988;2:168–177
  18. Carmel R, Rasmussen K, Jacobsen DW, Green R. Comparison of the deoxyuridine suppression test with serum levels of methylmalonic acid and homocysteine in mild cobalamin deficiency. Br J Haematol. 1996;93:311–318
  19. Chanarin I. The megaloblastic anaemias. third ed.. Oxford: Blackwell Scientific Publications; 1990;
  20. Jones P, Grace CS, Rozenberg MC. Interpretation of serum and red cell folate results. A comparison of microbiological and radioisotopic methods. Pathology. 1979;11:45–52
  21. Jaffe JP, Schilling RF. Erythrocyte folate levels: a clinical study. Am J Hematol. 1991;36:116–121
  22. Phekoo K, Williams Y, Schey SA, Andrews VE, Dudley JM, Hoffbrand AV. Folate assays: Serum or red cell?. J R Coll Physicians Lond. 1997;31:291–295
  23. Owen WE, Roberts WL. Comparison of five automated serum and whole blood folate assays. Am J Clin Pathol. 2003;120:121–126
  24. Clifford AJ, Noceti EM, Block-Joy A, Block T, Block G. Erythrocyte folate and its response to folic acid supplementation is assay dependent in women. J Nutr. 2005;135:137–143
  25. Bain BJ, Wickramasinghe SN, Broom GN, Litwinczuk RA, Sims J. Assessment of the value of a competitive protein binding radioassay of folic acid in the detection of folic acid deficiency. J Clin Pathol. 1984;37:888–894
  26. Schwartz SO, Kaplan SR, Armstrong BE. The long-term evaluation of folic acid in the treatment of pernicious anemia. J Lab Clin Med. 1950;35:894–898
  27. Carmel R. Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia and macrocytosis are often lacking. Arch Intern Med. 1988;148:1712–1714
  28. Thompson WG, Cassino C, Babitz L, et al. Hypersegmented neutrophils and vitamin B12 deficiency. Acta haematol. 1989;81:186–191
  29. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990;76:871–881
  30. Healton EB, Savage DG, Brust JCM, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine. 1991;70:229–245
  31. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. New Engl J Med. 1988;318:1720–1728
  32. Donnelly S, Callaghan N. Subacute combined degeneration of the spinal cord due to folate deficiency in association with a psychotic illness. Ir Med J. 1990;83:73–74
  33. Parry TE. Folate responsive neuropathy. Presse Med. 1994;23:131–137
  34. Ravakhah K, West BC. Case report: subacute combined degeneration of the spinal cord from folate deficiency. Am J Med Sci. 1995;310:214–216
  35. Guettat L, Gille M, Delbecq J, Depre A. Folic acid deficiency with leukoencephalopathy and chronic axonal neuropathy of sensory predominance. Rev Neurol (Paris). 1997;153:351–353
  36. Hsu CT, Miller NR, Wray ML. Optic neuropathy from folic acid deficiency without alcohol abuse. Ophthalmologica. 2002;216:65–67
  37. Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH. Depression and folate status in the US Population. Psychother Psychosom. 2003;72:80–87
  38. Bottiglieri T. Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:1103–1112
  39. Koebnick C, Hoffmann I, Dagnelie PC, Heins UA, Wickramasinghe SN, Ratnayaka ID, et al. Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women. J Nutr. 2004;134:3319–3326
  40. Herbert V. The 1986 Herman Award Lecture. Nutrition science as a continually unfolding story: The folate and vitamin B-12 paradigm. Am J Clin Nutr. 1987;46:387–402
  41. Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr. 1994;59(Suppl):1213S–1222S
  42. Carmel R. Subtle cobalamin deficiency. In:  Bhatt HR,  James VHT,  Besser GM, et al. editor. Advances in Thomas Addison’s Diseases. vol 1:Bristol: Journal of Endocrinology Ltd; 1994;p. 281–294
  43. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003;78:131–136
  44. Korenke GC, Hunneman DH, Eber S, Hanefeld F. Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: Case report and review of the literature. Eur J Pediatr. 2004;163:196–201
  45. Gutierrez-Aguilar G, Abenia-Uson P, Garcia-Cazorla A, Vilaseca MA, Campistol J. Encephalopathy with methylmalonic aciduria and homocystinuria secondary to a deficient exogenous supply of vitamin B12. Rev Neurol. 2005;40:605–608
  46. Doscherholmen A, McMahon J, Ripley D. Vitamin B12 assimilation from chicken meat. Am J Clin Nutr. 1978;31:825–830
  47. Carmel R, Sinow RM, Siegel ME, Samloff IM. Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels. Arch Intern Med. 1988;148:1715–1719
  48. Miller A, Furlong D, Burrows BA, Slingerland DW. Bound vitamin B12 absorption in patients with low serum B12 levels. Am J Hematol. 1992;40:163–166
  49. Carmel R. Cobalamin, the stomach, and aging. Am J Clin Nutr. 1997;66:750–759
  50. Dawson DW, Sawers AH, Sharma RK. Malabsorption of protein bound vitamin B12. Br Med J. 1984;288:675–678
  51. Carmel R, Sinow RM, Karnaze DS. Atypical cobalamin deficiency. Subtle biochemical evidence of deficiency is commonly demonstrable in patients without megaloblastic anemia and is often associated with protein-bound cobalamin malabsorption. J Lab Clin Med. 1987;109:454–463
  52. Jones BP, Broomhead AF, Kwan YL, Grace CS. Incidence and clinical significance of protein-bound vitamin B12 malabsorption. Eur J Haematol. 1987;38:131–136
  53. Karnaze DS, Carmel R. Neurologic and evoked potential abnormalities in subtle cobalamin deficiency states, including deficiency without anemia and with normal absorption of free cobalamin. Arch Neurol. 1990;47:1008–1012
  54. Carmel R, Gott PS, Waters CH, Cairo K, Green R, Bondareff W, et al. The frequently low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities. Eur J Haematol. 1995;54:245–253
  55. King CE, Toskes PP. Evolution of protein-bound cobalamin malabsorption. Arch Intern Med. 1983;143:2219
  56. Andres E, Noel E, Henoun Loukili N, Coca C, Vinzio S, Blickle JF. Is there a link between the food-cobalamin malabsorption and the pernicious anemia?. Ann Endocrinol (Paris). 2004;65:118–120
  57. Andres E, Affenberger S, Vinzio S, Kurtz JE, Noel E, Kaltenbach G, et al. Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment. Am J Med. 2005;118:1154–1159
  58. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med. 2000;51:357–375
  59. Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med. 1996;156:1097–1100
  60. Carmel R. Pepsinogens and other serum markers in pernicious anemia. Am J Clin Pathol. 1988;90:442–445
  61. Kekki M, Samloff IM, Varis K, Ihamaki T. Serum pepsinogen I and serum gastrin in the screening of severe atrophic corpus gastritis. Scand J Gastroenterol Suppl. 1991;186:109–116
  62. Carmel R. Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: Influence of patient age and race. Clin Exp Immunol. 1992;89:74–77
  63. Carmel R. Gastric juice in congenital pernicious anemia contains no immunoreactive intrinsic factor molecule: Study of three kindreds with variable ages at presentation, including a patient first diagnosed in adulthood. Am J Hum Genet. 1983;35:67–77
  64. Rosenblatt D, Fenton WA. Inherited disorders of folate and cobalamin transport and metabolism. In:  Scriver CR,  Beaudet AL,  Sly WS,  Valle D,  Childs B,  Kinzler KW,  Vogelstein B editor. The metabolic & molecular bases of inherited disease. Eighth ed.. New york: McGraw-Hill; 2001;p. 3897–3933
  65. Gordon MM, Brada N, Remacha A, Badell I, del Rio E, Baiget M, et al. A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency. Hum Mutat. 2004;23:85–91
  66. Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, et al. Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A. 2005;102:4130–4133
  67. Katz M, Mehlman CS, Allen RH. Isolation and characterization of an abnormal human intrinsic factor. J Clin Invest. 1974;53:1274–1283
  68. Yang YM, Ducos R, Rosenberg AJ, Catrou PG, Levine JS, Podell ER, et al. Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis. J Clin Invest. 1985;76:2057–2065
  69. Dupouy-Camet J, Peduzzi R. Current situation of human diphyllobothriasis in Europe. Euro Surveill. 2004;9:31–35
  70. Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, de la Chapelle A, et al. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004;103:1573–1579
  71. Tanner SM, 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;23:327–333
  72. Burkes RL, Cohen H, Krailo M, Sinow RM, Carmel R. Low serum cobalamin levels occur frequently in the acquired immune deficiency syndrome and related disorders. Eur J Haematol. 1987;38:141–147
  73. Remacha AF, Riera A, Cadafalch J, Gimferrer E. Vitamin B-12 abnormalities in HIV-infected patients. Eur J Haematol. 1991;47:60–64
  74. Paltiel O, Falutz J, Veilleux M, Rosenblatt DS, Gordon K. Clinical correlates of subnormal vitamin B12 levels in patients infected with the human immunodeficiency virus. Am J Hematol. 1995;49:318–322
  75. Remacha AF, Cadafalch J. Cobalamin deficiency in patients infected with the human immunodeficiency virus. Semin Hematol. 1999;36:75–87
  76. Herzlich BC, Schiano TD, Moussa Z, Zimbalist E, Panagopoulos G, Ast A, et al. Decreased intrinsic factor secretion in AIDS: Relation to parietal cell acid secretory capacity and vitamin B12 malabsorption. Am J Gastroenterol. 1992;87:1781–1788
  77. Chanarin I. Cobalamins and nitrous oxide: A review. J Clin Pathol. 1980;33:909–916
  78. Layzer RB. Myeloneuropathy after prolonged exposure to nitrous oxide. Lancet. 1978;ii:1227–1230
  79. Nunn JF, Sharer NM, Gorchein A, Jones JA, Wickramasinghe SN. Megaloblastic haemopoiesis after multiple short-term exposure to nitrous oxide. Lancet. 1982;i:1379–1381
  80. Diamond AL, Diamond R, Freedman SM, Thomas FP. “Whippets”-induced cobalamin deficiency manifesting as cervical myelopathy. J Neuroimaging. 2004;14:277–280
  81. Doran M, Rassam SS, Jones LM, Underhill S. Toxicity after intermittent inhalation of nitrous oxide for analgesia. Br Med J. 2004;328:1364–1365
  82. Burman JF, Mollin DL, Sourial NA, Sladden RA. Inherited lack of transcobalamin II in serum and megaloblastic anaemia: A further patient. Br J Haematol. 1979;43:27–38
  83. Hall CA. The neurologic aspects of transcobalamin II deficiency. Br J Haematol. 1992;80:117–120
  84. Kaikov Y, Wadsworth LD, Hall CA, Rogers PC. Transcobalamin II deficiency: Case report and review of the literature. Eur J Pediatr. 1991;150:841–843
  85. Haurani FI, Hall CA, Rubin R. Megaloblastic anemia as a result of an abnormal transcobalamin II (Cardoza). J Clin Invest. 1979;64:1253–1259
  86. Seligman PA, Steiner LL, Allen RH. Studies of a patient with megaloblastic anemia and an abnormal transcobalamin II. N Engl J Med. 1980;303:1209–1212
  87. Qian L, Quadros EV, Regec A, Zittoun J, Rothenberg SP. Congenital transcobalamin II deficiency due to errors in RNA editing. Blood Cells Mol Dis. 2002;28:134–142discussion 143–5
  88. Namour F, Helfer A-C, Quadros EV, Alberto J-M, Bibi HM, Orning L, et al. Transcobalamin deficiency due to activation of an intra exonic cryptic splice site. Br J Haematol. 2003;123:915–920
  89. Linnell JC, Bhatt HR. Inherited errors of cobalamin metabolism and their management. Bailliere’s Clin Haematol. 1995;8/3:567–601
  90. Green R, Miller JW. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population. Clin Chem Lab Med. 2005;43:1048–1051
  91. Scott JM, Weir DG. Drug-induced megaloblastic change. Clin Haematol. 1980;9:587–606
  92. Reynolds EH, Laundy M. Haematological effects of anticonvulsant treatment. Lancet. 1978;ii:682
  93. Sutterlin MW, Bussen SS, Rieger L, Dietl J, Steck T. Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. Eur J Obstet Gynecol Reprod Biol. 2003;107:57–61
  94. Green TJ, Houghton LA, Donovan U, Gibson RS, O’Connor DL. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc. 1998;98:49–55
  95. Gardyn J, Mittelman M, Zlotnik J, Sela BA, Cohen AM. Oral contraceptives can cause falsely low vitamin B(12) levels. Acta Haematol. 2000;104:22–24
  96. Zittoun J. Congenital errors of folate metabolism. Bailliere’s Clin Haematol. 1995;8/3:603–616
  97. Hilton JF, Christensen KE, Watkins D, Raby BA, Renaud Y, de la Luna S, et al. The molecular basis of glutamate formiminotransferase deficiency. Hum Mutat. 2003;22:67–73
  98. Girot R, Hamet M, Perignon J-L, Guesnu M, Fox RM, Cartier P, et al. Cellular immune deficiency in two siblings with hereditary orotic aciduria. N Engl J Med. 1983;308:700–704
  99. Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005;86:25–33
  100. Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, et al. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet. 1997;60:525–539
  101. Salerno C, Crifo C. Diagnostic value of urinary orotic acid levels: Applicable separation methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;781:57–71
  102. Nyhan WL. The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. J Inherit Metab Dis. 1997;20:171–178
  103. Nyhan WL. Lesch-Nyhan Disease. J Hist Neurosci. 2005;14:1–10
  104. van der Zee SPM, Schretlen EDAM, Monnens LAH. Megaloblastic anaemia in the Lesch-Nyhan syndrome. (Letter) Lancet. 1968;i:1427
  105. Cossu A, Orru S, Jacomelli G, Carcassi C, Contu L, Sestini S, et al. HPRT (Sardinia): A new point mutation causing HPRT deficiency without Lesch-Nyhan disease. Biochim Biophys Acta. 2005;1762:29–33
  106. Wickramasinghe SN, Hasan R. Possible role of macrophages in the pathogenesis of ethanol-induced bone marrow damage. Br J Haematol. 1993;83:574–579
  107. Wickramasinghe SN. Role of macrophages in the pathogenesis of alcohol-induced tissue damage. Br Med J. 1987;294:1137–1139
  108. Wickramasinghe SN, Gardner B, Barden G. Circulating cytotoxic protein generated after ethanol consumption: Identification and mechanism of reaction with cells. Lancet. 1987;ii:122–126
  109. Wickramasinghe SN, Wood WG. Advances in the understanding of the congenital dyserythropoietic anaemias. Br J Haematol. 2005;131:431–446
  110. Haworth C, Evans DIK, Mitra J, Wickramasinghe SN. 1982 Thiamine responsive anaemia: A study of two further cases. Br J Haematol. 1982;50:549–561
  111. Fleming JC, Tartaglini E, Steinkamp MP, Schorderet DF, Cohen N, Neufeld EJ. The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Nat Genet. 1999;22:305–308
  112. Diaz GA, Banikazemi M, Oishi K, Desnick RJ, Gelb BD. Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. Nat Genet. 1999;22:309–312
  113. 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;22:300–304

PII: S0268-960X(06)00015-4

doi: 10.1016/j.blre.2006.02.002

Blood Reviews
Volume 20, Issue 6 , Pages 299-318 , November 2006