scholarly journals Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: A clinical study based on gastrointestinal histopathological findings

1997 ◽  
Vol 56 (4) ◽  
pp. 230-238 ◽  
Author(s):  
Anders Lindgren ◽  
Birgitta Swolin ◽  
Ola Nilsson ◽  
Kurt W. Johansson ◽  
Anders F. Kilander
Keyword(s):  
Clinical Study ◽  
Methylmalonic Acid ◽  
Cobalamin Deficiency ◽  
Histopathological Findings ◽  
Total Homocysteine

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

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.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

Abstract 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.

Evaluation of Indicators of Cobalamin Deficiency Defined as Cobalamin-induced Reduction in Increased Serum Methylmalonic Acid

2000 ◽  
Vol 46 (11) ◽  
pp. 1744-1750 ◽  
Author(s):  
Bjørn J Bolann ◽  
Jan Dag Solli ◽  
Jörn Schneede ◽  
Kjell A Grøttum ◽  
Arne Loraas ◽  
...  
Keyword(s):  
General Practice ◽  
Methylmalonic Acid ◽  
Intrinsic Factor ◽  
Cobalamin Deficiency ◽  
Additional Information ◽  
Erythrocyte Folate ◽  
Total Homocysteine ◽  
And Gender ◽  
Age Range

Abstract Background: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. Methods: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17–87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 μmol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used. Results: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0.810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information. Conclusions: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.

Diagnosis of cobalamin deficiency I: Usefulness of serum methylmalonic acid and total homocysteine concentrations

1990 ◽  
Vol 34 (2) ◽  
pp. 90-98 ◽  
Author(s):  
Robert H. Allen ◽  
Sally P. Stabler ◽  
David G. Savage ◽  
John Lindenbaum
Keyword(s):  
Methylmalonic Acid ◽  
Cobalamin Deficiency ◽  
Total Homocysteine

scholarly journals Cobalamin (vitamin B12) deficiency detection by urinary methylmalonic acid quantitation

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1128-1131 ◽  
Author(s):  
EJ Norman ◽  
OJ Martelo ◽  
MD Denton
Keyword(s):  
Methylmalonic Acid ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Cobalamin Deficiency ◽  
Clinical Test ◽  
Test Results ◽  
Neurologic Disorders ◽  
Schilling Test ◽  
B12 Deficiency ◽  
And Function

Abstract A study was made to assess the value of cobalamin deficiency detection through quantitation of urinary methylmalonic acid (MMA). Urinary MMA was measured in 1118 patients suffering from megaloblastic anemia, other anemias, elevated red cell mean corpuscular volume, or unexplained neurologic disorders. Patients without proven cobalamin deficiency had urinary MMA levels less than 20 micrograms/ml. All patients (n = 27) confirmed to have cobalamin deficiency showed MMA levels greater than 20 micrograms/ml. Data are presented showing the Schilling test results, the comparison of serum cobalamin to urinary MMA levels, and other basic hematologic data. MMA levels are a good indication of cobalamin distribution and function since they are directly related to a cobalamin-dependent metabolic pathway. With rapid, reliable quantitation by mass spectrometry, urinary MMA can now be a useful clinical test.

scholarly journals External Quality Assessment of Methylmalonic Acid and Total Homocysteine

1999 ◽  
Vol 45 (9) ◽  
pp. 1536-1542 ◽  
Author(s):  
Jan Møller ◽  
Karsten Rasmussen ◽  
Lene Christensen
Keyword(s):  
Gas Chromatography ◽  
Quality Assessment ◽  
Methylmalonic Acid ◽  
External Quality Assessment ◽  
Mass Spectrometric ◽  
External Quality ◽  
Laboratory Component ◽  
Edta Plasma ◽  
Total Homocysteine ◽  
Minimum Quality

Abstract Background: The use of analyses for methylmalonic acid (MMA) and total homocysteine (HCY) in plasma has become widespread. Realizing the need for external quality assessment for these measurements, we started a program in 1997. The results for 1998 are reviewed in this report. Methods: Fourteen laboratories participated with 15 sets of results for MMA, and 28 laboratories participated with 34 sets of results for HCY. Results for four identical samples, made up from the same unmodified serum (MMA) or EDTA-plasma (HCY) pool, sent out under different identifications, were used for assessing the imprecision. Samples made up from the same pools supplemented with MMA or l-HCY to three concentrations were used for assessing the recovery. By using literature data for the biological variation, quality goals for both analytes were calculated. Results: The overall within-laboratory CV was 12% for MMA and 7.5% for HCY. Gas chromatography–mass spectrometric HCY results had lower imprecision than the HPLC or immunoassay results. For MMA, no significant between-laboratory component of variance was found. Only results for HCY obtained with HPLC methods showed significant between-laboratory variance. Conclusions: Eight of the 15 participants achieved the minimum imprecision goal for MMA vs 9 of the 34 participants for HCY. The minimum quality goals for bias as approximated by the recovery were achieved by 13 participants for MMA and 26 for HCY.

Solid-phase sample extraction for rapid determination of methylmalonic acid in serum and urine by a stable-isotope-dilution method.

1989 ◽  
Vol 35 (2) ◽  
pp. 260-264 ◽  
Author(s):  
K Rasmussen
Keyword(s):  
Methylmalonic Acid ◽  
Solid Phase ◽  
Rapid Determination ◽  
Current Method ◽  
Reference Interval ◽  
Cobalamin Deficiency ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Selected Ion Monitoring

Abstract Methylmalonic acid concentrations are increased in serum in vitamin B12 (cobalamin) deficiency. Here I demonstrate the successful use of anion-exchange extraction for improving newly developed analytical procedures and describe well-documented, reliable performance of this method for rapid determination of methylmalonic acid. The sorbent counter ion is formate, and the elution solvent is formic acid. The dicyclohexyl derivative is measured by selected ion monitoring. For serum, the assay curve is linear from 0.026 to 200 mumol/L. The normal reference interval is 0.08 to 0.56 mumol/L. Added methylmalonic acid is accurately quantified. The sensitivity and the precision exceed those of the current method by three orders of magnitude. The total and within-day CVs are 4.6% to 7.9% and 2.6% to 4.7%, respectively. Similar figures were obtained for urine. This convenient method is useful for evaluation of cobalamin deficiency, especially in patients with normal or moderately depressed cobalamin concentrations in serum.

Sign in / Sign up

Export Citation Format

Share Document