|
|
Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-09-2746.
 Previous Article | Table of Contents | Next Article 
Blood, 15 April 2003, Vol. 101, No. 8, pp. 3302-3308
RED CELLS
Cobalamin deficiency with and without neurologic abnormalities:
differences in homocysteine and methionine
metabolism
Ralph Carmel,
Stepan Melnyk, and
S. Jill James
From the Departments of Medicine, New York Methodist
Hospital, Brooklyn, NY, and Weill Medical College of Cornell
University, New York, NY; and Division of Biochemical Toxicology,
National Center for Toxicological Research, Jefferson, AR.
The unknown biochemical basis for neurologic dysfunction in
cobalamin deficiency and the frequent divergence between neurologic and
hematologic manifestations led us to study homocysteine metabolism in
22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet),
cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were
measured. Only levels of tHcy and cysteine were increased and only GSH
was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels
(P = .015) and cysteine only with cys-gly
(P = .007) in healthy subjects, but in
cobalamin-deficient patients AdoMet correlated instead with cysteine,
cys-gly, and folate levels only (P = .008,
P = .03, and P = .03, respectively). Significant differences appeared in clinically subgrouped
cobalamin-deficient patients. The 11 patients with neurologic defects
had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 µM), and cys-gly (85.0 versus 54.7 µM) than the 11 neurologically unaffected patients.
Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients
with and without neurologic dysfunction. Cysteine levels were the most
significant predictors of neurologic dysfunction, but it is unclear if
they are direct or indirect indicators of neurotoxicity. The higher
AdoMet levels in neurologically affected patients may result from
inhibition of glycine N-methyltransferase by those
patients' higher folate levels. The origin of the folate differences
is unclear and possibly varied. Low AdoMet and GSH levels were
independent predictors of anemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
W.-y. Au, S.-K. Tsang, B. K.L. Cheung, T.-S. Siu, E. S.K. Ma, and S. Tam
Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study
Haematologica,
April 1, 2007;
92(4):
562 - 563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W. Marks and L. R. Zukerberg
Case 30-2004 - A 37-Year-Old Woman with Paresthesias of the Arms and Legs
N. Engl. J. Med.,
September 23, 2004;
351(13):
1333 - 1341.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dhar, R. Bellevue, and R. Carmel
Pernicious Anemia with Neuropsychiatric Dysfunction in a Patient with Sickle Cell Anemia Treated with Folate Supplementation
N. Engl. J. Med.,
May 29, 2003;
348(22):
2204 - 2207.
[Full Text]
[PDF]
|
|
|
| |
