Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.

1989 ◽  
Vol 35 (12) ◽  
pp. 2271-2276 ◽  
Author(s):  
K Rasmussen
Keyword(s):  
Urinary Excretion ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Cobalamin Deficiency ◽  
Absolute Amount ◽  
Ambulatory Patients ◽  
B12 Deficiency ◽  
First Time

Abstract Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients.

Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.

1989 ◽  
Vol 35 (12) ◽  
pp. 2277-2280 ◽  
Author(s):  
K Rasmussen ◽  
L Moelby ◽  
M K Jensen
Keyword(s):  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Cobalamin Deficiency ◽  
Serum Samples ◽  
Linear Relationships ◽  
Diagnostic Usefulness ◽  
B12 Deficiency ◽  
Excretion Rates ◽  
Hematological Evaluation ◽  
First Time

Abstract Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005).

scholarly journals Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 125-137
Author(s):  
EP Frenkel ◽  
RL Kitchens
Keyword(s):  
Propionic Acid ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Methylmalonic Aciduria ◽  
Assay Method ◽  
Partial Purification ◽  
Etiologic Factor ◽  
Acid Excretion ◽  
B12 Deficiency

A rapid sensitive spectrophotometric assay for the measurement of methylmalonic and propionic acids in urine is described. The assay is based upon the quantitation of propionic acid using acetyl coenzyme A synthetase isolated from baker's yeast. This enzyme is highly specific for acetate and propionate, and acetate interference is eliminated by conversion to citrate. Methylmalonic acid was assayed by converting it to propionate by heat decarboxylation and then measuring the propionate increment over the endogenous amount in the noncarboxylated sample. Studies of urine obtained from normal subjects (by isolation, partial purification, and then assay by the isotope dilution technique) demonstrated urinary excretion of less than 1 mg of propionic acid and 1–5 mg of methylmalonic acid per day. In 22 consecutive patients with documented vitamin B12 deficiency, methylmalonic acid excretion in excess of 30 mg/24 hr was found. In four other patients, with only neurologic involvement methylmalonic aciduria aided in identifying B12 deficiency as an etiologic factor. Methylmalonic acid excretion was measured by direct assay of an aliquot of urine, requiring neither a valine load nor special extraction procedures. Propionic aciduria was variably increased in B12 deficiency and did not correlate either with the severity of the deficit or degree of methylmalonic aciduria. The assay was performed on urine, but it is potentially applicable to tissue extracts. In addition, this assay method can be utilized for the quantification of urine acetate levels as well.

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 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

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 High frequency of vitamin B12 deficiency in a Brazilian population

2010 ◽  
Vol 13 (8) ◽  
pp. 1191-1197 ◽  
Author(s):  
JM Xavier ◽  
FF Costa ◽  
JM Annichino-Bizzacchi ◽  
STO Saad
Keyword(s):  
High Frequency ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Cobalamin Deficiency ◽  
Vitamin B ◽  
Mean Cell Volume ◽  
Adult Participants ◽  
B12 Deficiency ◽  
Older Subjects ◽  
Brazilian Populations

AbstractObjectiveThere are few studies regarding vitamin B12 deficiency in developing countries. In Brazil, a late diagnosis of vitamin B12 deficiency progressing to severe neurological damage is common. Thus, the aim of the present study was to verify the frequency of vitamin B12 deficiency in two Brazilian populations (elderly and adult participants) and to compare different methods of vitamin B12 deficiency detection.DesignFive hundred participants were recruited from health centres from south-east Brazil and were separated into two groups: 60 years old or more and 30–59 years old. Vitamin B12 and folate concentrations were measured using electrochemiluminescence immunoassay (ECI) and RIA. Methylmalonic acid (MMA) was measured by LC coupled to tandem MS. Full blood counts were acquired using standard methods.ResultsAll participants had normal blood count results and mean cell volume less than 99 fl; none of them presented folate deficiency according to the results, which were all greater than 3 ng/ml. Cobalamin levels less than 200 pmol/l were identified by one of the two or by both methods in 7·2 % of the participants aged 60 years or more and 6·4 % of the participants aged 30–59 years. MMA levels were higher in older subjects (P = 0·007) compared with younger subjects. A greater correlation of MMA v. RIA was observed than of MMA v. ECI (P = 0·0017 v. P = 0·014). MMA quantification estimated that cobalamin deficiency was present in more than 11 % of the subjects for both studied groups.ConclusionsThe study shows that vitamin B12 deficiency is frequent in Brazilian adults and suggests that RIA is more sensitive than ECl for measuring cobalamin levels.

scholarly journals Vitamin B12 deficiency and the excretion of ether-soluble acids in the rat

1967 ◽  
Vol 21 (2) ◽  
pp. 309-314 ◽  
Author(s):  
B. K. Armstrong
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Vitamin B ◽  
B12 Deficiency ◽  
Males And Females

1. Urinary excretion of total ether-soluble acids and of methylmalonic acid was studied in rats on vitamin B12-deficient diets with and without a vitamin B12 supplement.2. It was shown that urinary excretion of total ether-soluble acids and methylmalonic acid was increased in vitamin B12-deficient rats and that this increase was somewhat variable between individual animals, males and females, and rats from different litters.3. The increased excretion of these acids could readily be reversed by supplementing the diet with vitamin B12.

scholarly journals The Plasma Clearance and Urinary Excretion of Parenterally Administered 58Co B12

Blood ◽  
1956 ◽  
Vol 11 (1) ◽  
pp. 31-43 ◽  
Author(s):  
D. L. MOLLIN ◽  
W. R. PITNEY ◽  
S. J. BAKER ◽  
J. E. BRADLEY
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Plasma Clearance ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Normal Serum ◽  
Chronic Myelocytic Leukemia ◽  
Intravenous Injections ◽  
Myelocytic Leukemia ◽  
B12 Deficiency

Abstract Intravenous injections of 1.5 µg. of 58Co B12 were given to subjects with normal serum B12 concentrations, to patients with vitamin B12 deficiency and to patients with chronic myelocytic leukemia. The rate of plasma clearance of radioactivity after this dose was slowest in patients with chronic myelocytic leukemia and patients with pernicious anemia in severe relapse. In patients with vitamin B12 deficiency, serum B12 concentrations were estimated microbiologically at frequent intervals after the injection. There was a good correlation between the results obtained by microbiological assay and as calculated from plasma radioactivity. Significant differences were not observed between the urinary excretion of radioactivity by normal subjects and patients with B12 deficiency.

scholarly journals Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents

2021 ◽  
Author(s):  
M. Rebecca Heiner-Fokkema ◽  
Ineke J. Riphagen ◽  
Nicole S. Wiersema ◽  
Jelmer J. van Zanden ◽  
Jenny E. Kootstra-Ros ◽  
...  
Keyword(s):  
Young Children ◽  
Vitamin B12 ◽  
Reference Values ◽  
Methylmalonic Acid ◽  
Early Recognition ◽  
Vitamin B12 Deficiency ◽  
Reference Intervals ◽  
Cobalamin Deficiency ◽  
Plasma Vitamin ◽  
B12 Deficiency

Abstract Background Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals. Methods Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. Results Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. Conclusions Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. Impact We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.

scholarly journals Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 125-137 ◽  
Author(s):  
EP Frenkel ◽  
RL Kitchens
Keyword(s):  
Propionic Acid ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Methylmalonic Aciduria ◽  
Assay Method ◽  
Partial Purification ◽  
Etiologic Factor ◽  
Acid Excretion ◽  
B12 Deficiency

Abstract A rapid sensitive spectrophotometric assay for the measurement of methylmalonic and propionic acids in urine is described. The assay is based upon the quantitation of propionic acid using acetyl coenzyme A synthetase isolated from baker's yeast. This enzyme is highly specific for acetate and propionate, and acetate interference is eliminated by conversion to citrate. Methylmalonic acid was assayed by converting it to propionate by heat decarboxylation and then measuring the propionate increment over the endogenous amount in the noncarboxylated sample. Studies of urine obtained from normal subjects (by isolation, partial purification, and then assay by the isotope dilution technique) demonstrated urinary excretion of less than 1 mg of propionic acid and 1–5 mg of methylmalonic acid per day. In 22 consecutive patients with documented vitamin B12 deficiency, methylmalonic acid excretion in excess of 30 mg/24 hr was found. In four other patients, with only neurologic involvement methylmalonic aciduria aided in identifying B12 deficiency as an etiologic factor. Methylmalonic acid excretion was measured by direct assay of an aliquot of urine, requiring neither a valine load nor special extraction procedures. Propionic aciduria was variably increased in B12 deficiency and did not correlate either with the severity of the deficit or degree of methylmalonic aciduria. The assay was performed on urine, but it is potentially applicable to tissue extracts. In addition, this assay method can be utilized for the quantification of urine acetate levels as well.

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