|
|
 Previous Article | Table of Contents | Next Article 
Clinical spectrum and diagnosis of cobalamin deficiency [see comments]
SP Stabler, RH Allen, DG Savage and J Lindenbaum
Department of Medicine, University of Colorado Health Sciences Center,
Denver 80262.
To better estimate how frequently patients with low serum cobalamin (Cbl)
levels in current clinical practice are truly deficient in Cbl and to
determine the incidence of atypical or nonclassic presentations of Cbl
deficiency, we prospectively studied 300 unselected consecutive patients
with serum Cbl concentrations less than 200 pg/mL seen at two medical
centers over a 2-year period. Baseline hematologic, neuropsychiatric, and
biochemical measurements were obtained, followed by a course of parenteral
Cbl therapy and reassessment. A response to Cbl therapy was defined as one
or more of the following: (1) an increase in hematocrit of 0.05 or more;
(2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of
hypersegmented neutrophilis and macroovalocytes from the peripheral blood
smear; and (4) an unequivocal and prompt improvement of neuropsychiatric
abnormalities. Of the 300 patients with serum Cbl levels less than 200
pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response.
In 155, insufficient data was available. In the Cbl-responsive patients,
normal values were found for the following tests: hematocrit, 44%; mean
cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%;
platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin,
83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the
investigators, but 33% as reported by routine laboratories. Serum Cbl
levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric
abnormalities were noted in 28%, often in the absence of anemia,
macrocytosis, or both. Serum levels of methylmalonic acid and/or total
homocysteine were elevated greater than 3 SDs above the mean for normal
subjects in 94% of the Cbl-responsive patients. We conclude that Cbl
deficiency should be considered and investigated in patients with
unexplained hematologic or neuropsychiatric abnormalities of the kind seen
in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked
depression of the serum Cbl, or other classic hematologic or biochemical
abnormalities are lacking. Levels of serum methylmalonic acid and total
homocysteine are useful as ancillary diagnostic tests in the diagnostis of
Cbl deficiency.
Volume 76,
Issue 5,
pp. 871-881,
09/01/1990
Copyright © 1990 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Dali-Youcef and E. Andres
An update on cobalamin deficiency in adults
QJM,
January 1, 2009;
102(1):
17 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. P. J. den Elzen, R. G. J. Westendorp, M. Frolich, W. de Ruijter, W. J. J. Assendelft, and J. Gussekloo
Vitamin B12 and Folate and the Risk of Anemia in Old Age: The Leiden 85-Plus Study
Arch Intern Med,
November 10, 2008;
168(20):
2238 - 2244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Iverson, M. McKenzie, K. Juhasz-Pocsine, S. A. Rudnicki, R. L. Archer, and S. I. Harik
NEUROLOGIC COMPLICATIONS OF GASTRIC BYPASS SURGERY FOR MORBID OBESITY
Neurology,
January 22, 2008;
70(4):
324 - 325.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galloway and M. Hamilton
Macrocytosis: pitfalls in testing and summary of guidance
BMJ,
October 27, 2007;
335(7625):
884 - 886.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tettamanti, M. T. Garri, A. Nobili, E. Riva, and U. Lucca
Low Folate and the Risk of Cognitive and Functional Deficits in the Very Old: The Monzino 80-plus Study
J. Am. Coll. Nutr.,
December 1, 2006;
25(6):
502 - 508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ingenbleek
The Nutritional Relationship Linking Sulfur to Nitrogen in Living Organisms
J. Nutr.,
June 1, 2006;
136(6):
1641S - 1651S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Vlasveld, J. W. van't Wout, P. Meeuwissen, and A. Castel
High Measured Cobalamin (Vitamin B12) Concentration Attributable to an Analytical Problem in Testing Serum from a Patient with Pernicious Anemia
Clin. Chem.,
January 1, 2006;
52(1):
157 - 158.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W S A Smellie, D Wilson, C A M McNulty, M J Galloway, G A Spickett, D I Finnigan, D A Bareford, M A Greig, and J Richards
Best practice in primary care pathology: review 1
J. Clin. Pathol.,
October 1, 2005;
58(10):
1016 - 1024.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Carmel and L. R. Solomon
Is testing for clinical cobalamin deficiency truly unreliable?
Blood,
August 1, 2005;
106(3):
1136 - 1138.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. R. Solomon
Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing
Blood,
February 1, 2005;
105(3):
978 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tolmunen, J. Hintikka, S. Voutilainen, A. Ruusunen, G. Alfthan, K. Nyyssonen, H. Viinamaki, G. A Kaplan, and J. T Salonen
Association between depressive symptoms and serum concentrations of homocysteine in men: a population study
Am. J. Clinical Nutrition,
December 1, 2004;
80(6):
1574 - 1578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Andres, N. H. Loukili, E. Noel, G. Kaltenbach, M. B. Abdelgheni, A. E. Perrin, M. Noblet-Dick, F. Maloisel, J.-L. Schlienger, and J.-F. Blickle
Vitamin B12 (cobalamin) deficiency in elderly patients
Can. Med. Assoc. J.,
August 3, 2004;
171(3):
251 - 259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al.
Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion
Clin. Chem.,
January 1, 2004;
50(1):
3 - 32.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Roze, D. Gervais, S. Demeret, H. Ogier de Baulny, J. Zittoun, J.-F. Benoist, G. Said, C. Pierrot-Deseilligny, and F. Bolgert
Neuropsychiatric Disturbances in Presumed Late-Onset Cobalamin C Disease
Arch Neurol,
October 1, 2003;
60(10):
1457 - 1462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tolmunen, S. Voutilainen, J. Hintikka, T. Rissanen, A. Tanskanen, H. Viinamaki, G. A. Kaplan, and J. T. Salonen
Dietary Folate and Depressive Symptoms Are Associated in Middle-Aged Finnish Men
J. Nutr.,
October 1, 2003;
133(10):
3233 - 3236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C Antony
Vegetarianism and vitamin B-12 (cobalamin) deficiency
Am. J. Clinical Nutrition,
July 1, 2003;
78(1):
3 - 6.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Bunting and M. K. Selig
Localization of DNA in Ultrascopic Nuclear Appendages of Polymorphonuclear White Blood Cells from Patients with Low Serum B12
J. Histochem. Cytochem.,
October 1, 2002;
50(10):
1381 - 1388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Morris, P. F. Jacques, I. H. Rosenberg, and J. Selhub
Elevated Serum Methylmalonic Acid Concentrations Are Common among Elderly Americans ,
J. Nutr.,
September 1, 2002;
132(9):
2799 - 2803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Weiss, C. Keller, U. Hoffmann, and J. Loscalzo
Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia
Vascular Medicine,
August 1, 2002;
7(3):
227 - 239.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Koebnick, U. A. Heins, P. C. Dagnelie, S. N. Wickramasinghe, I. D. Ratnayaka, T. Hothorn, A. B. Pfahlberg, I. Hoffmann, J. Lindemans, and C. Leitzmann
Longitudinal Concentrations of Vitamin B12 and Vitamin B12-binding Proteins during Uncomplicated Pregnancy
Clin. Chem.,
June 1, 2002;
48(6):
928 - 933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Reynish, S. Andrieu, F. Nourhashemi, and B. Vellas
Nutritional Factors and Alzheimer's Disease
J. Gerontol. A Biol. Sci. Med. Sci.,
November 1, 2001;
56(11):
M675 - 680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-L. B. Monsen, P. M. Ueland, S. E. Vollset, A. B. Guttormsen, T. Markestad, E. Solheim, and H. Refsum
Determinants of Cobalamin Status in Newborns
Pediatrics,
September 1, 2001;
108(3):
624 - 630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-M. Hvas, J. Ellegaard, and E. Nexo
Vitamin B12 Treatment Normalizes Metabolic Markers But Has Limited Clinical Effect: A Randomized Placebo-controlled Study
Clin. Chem.,
August 1, 2001;
47(8):
1396 - 1404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Rosner, H. W. Grunwald, J. S. Tobias, C. L. Carpenter, and R. E. Scully
Case 40-2000: Gastric Cancer in a Young Woman
N. Engl. J. Med.,
June 21, 2001;
344(25):
1949 - 1950.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Deleu, Y. Hanssens, A. Louon, and R.-M. Marie
Nitrous Oxide-Induced Cobalamin Deficiency
Arch Neurol,
January 1, 2001;
58(1):
134 - 135.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Carpenter and E. D. Patalas
Case 40-2000- A 38-Year-Old Woman with Gastric Adenocarcinoma
N. Engl. J. Med.,
December 28, 2000;
343(26):
1951 - 1958.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-C. Minet, E. Bisse, C.-P. Aebischer, A. Beil, H. Wieland, and J. Lutschg
Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur amino acid metabolism in neonates
Am. J. Clinical Nutrition,
September 1, 2000;
72(3):
751 - 757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Goebels and M. Soyka
Dementia Associated With Vitamin B12 Deficiency: Presentation of Two Cases and Review of the Literature
J Neuropsychiatry Clin Neurosci,
August 1, 2000;
12(3):
389 - 394.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J.-C. Essama-Tjani, J.-C. Guilland, G. Potier de Courcy, F. Fuchs, and D. Richard
Folate Status Worsens in Recently Institutionalized Elderly People without Evidence of Functional Deterioration
J. Am. Coll. Nutr.,
June 1, 2000;
19(3):
392 - 404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W.J.H. Penninx, J. M. Guralnik, L. Ferrucci, L. P. Fried, R. H. Allen, and S. P. Stabler
Vitamin B12 Deficiency and Depression in Physically Disabled Older Women: Epidemiologic Evidence From the Women's Health and Aging Study
Am J Psychiatry,
May 1, 2000;
157(5):
715 - 721.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. P Stabler, R. H Allen, L. P Fried, M. Pahor, S. J Kittner, B. W. Penninx, and J. M Guralnik
Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women
Am. J. Clinical Nutrition,
November 1, 1999;
70(5):
911 - 919.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. H Haddad, L. S Berk, J. D Kettering, R. W Hubbard, and W. R Peters
Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians
Am. J. Clinical Nutrition,
September 1, 1999;
70(3):
586S - 593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. G. van Walraven and C. D. Naylor
Use of vitamin B12 injections among elderly patients by primary care practitioners in Ontario
Can. Med. Assoc. J.,
July 1, 1999;
161(2):
146 - 149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Snow
Laboratory Diagnosis of Vitamin B12 and Folate Deficiency: A Guide for the Primary Care Physician
Arch Intern Med,
June 28, 1999;
159(12):
1289 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Harris, C. B. Saper, C. Anderson, M. Cole, Y. Elad, P. J. Nelson, and D. E. Meier
Clinical Problem-Solving: Diagnosis of Tuberculous Meningitis
N. Engl. J. Med.,
April 1, 1999;
340(13):
1047 - 1049.
[Full Text]
|
|
|
|
|
|
|
A. M. Kuzminski, E. J. Del Giacco, R. H. Allen, S. P. Stabler, and J. Lindenbaum
Effective Treatment of Cobalamin Deficiency With Oral Cobalamin
Blood,
August 15, 1998;
92(4):
1191 - 1198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Majors, L. A. Ehrhart, and E. H. Pezacka
Homocysteine as a Risk Factor for Vascular Disease : Enhanced Collagen Production and Accumulation by Smooth Muscle Cells
Arterioscler. Thromb. Vasc. Biol.,
October 1, 1997;
17(10):
2074 - 2081.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. R. McLean, E. V. Quadros, S. P. Rothenberg, A. C. Morgan, J. W. Schrader, and H. J. Ziltener
Antibodies to Transcobalamin II Block In Vitro Proliferation of Leukemic Cells
Blood,
January 1, 1997;
89(1):
235 - 242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Carr, J. M. Raya, M. N. Lowenthal, and S. Moll
Megaloblastosis
N. Engl. J. Med.,
December 26, 1996;
335(26):
2000 - 2001.
[Full Text]
|
|
|
|
|
|
|
Y. Yao, G. Lu-Yao, D. N. Mesches, and W. Lou
Decline of Serum Cobalamin Levels With Increasing Age Among Geriatric Outpatients
Arch Fam Med,
October 1, 1994;
3(10):
918 - 922.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. E. Goodkin, D. W. Jacobsen, and R. Green
Biologically Significant Serum Vitamin B12 Deficiency in Multiple Sclerosis Inadequately Documented
Arch Neurol,
July 1, 1992;
49(7):
683 - 683.
[Abstract]
[PDF]
|
|
|
|
|
