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At least 19 recordsLinked to original sources
PubMed1977

A technique for measurement of methylmalonic acid in cattle urine.

Methylmalonic acid was measured in cattle urine by decarboxylating it to propionate with sulfuric acid and heat and quantifying the propionate so formed by gas-liquid chromatography. Crystalline methylmalonic acid added to cow urine was recovered quantitatively.

Animals↗
PubMed1976

Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography: use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia.

We have developed a sensitive gas-chromatographic method for the determination of methylmalonic acid and other short chain dircarboxylic acids in biological samples. The method is based on the isolation of the short chain dicarboxylic acid fraction by Dowex 3 X 4 column chromatography followed by gas-chromatography analysis of these acids as methyl esters. 2-n-Pentyl-malonic acid is used as an internal standard. With this method, methylmalonic, succinic and methylsuccinic acids were consistently detected and accurately measured in urine and serum from normal subjects; the identity of these acids being verified by mass spectroscopy. The method's sensitivity permitted its used in the prenatal diagnosis of methylmalonic acidemia by measuring methylmalonic acid in urine and amniotic fluid from three pregnant heterozygous women at risk. One affected (vitamin B-12 responsive type) and two unaffected fetuses were correctly diagnosed prenatally as judged by postnatal investigations. The amount of methylmalonic acid in urine and amniotic fluid was distinctly increased (2 to 14 times normal) in the former and consistently normal in the latter two cases during the third trimester of pregnancy. Effect of prenatal therapy with large doses of vitamin B-12 was closely followed in the first case using analyses of multiple maternal urine specimens. Urinary methylsuccinic acid excretion was studied in two cases with isovaleric acidemia. It was normal in a sample from a patient in remission but was increased seven fold over control during an episode of ketoacidosis.

Adult↗
PubMed1992

Serum methylmalonic acid in uraemia.

During a 3 month period we measured serum methylmalonic acid concentrations monthly in 37 patients, all on chronic haemodialysis because of end-stage kidney disease. Concentrations of methylmalonic acid in serum were above the upper reference limit in 36 of the 37 subjects. All patients were in regular cobalamin therapy, with intramuscular injections every third month, and all had normal to very high values of serum cobalamin. We found no normalization of serum methylmalonic acid during the examination period after cobalamin injections, and we could not demonstrate any relationship between concentrations of methylmalonic acid and creatinine, cobalamin and creatinine or methylmalonic acid and cobalamin in serum of these subjects. We conclude that an elevated serum methylmalonic acid concentration is a general finding in uraemic patients, and so the assay cannot be used to establish the diagnosis of tissue cobalamin deficiency in these patients.

Adolescent↗
PubMed1979

Rapid thin-layer chromatographic method for the detection of urinary methylmalonic acid.

1. Simple and rapid thin-layer and micro-thin-layer chromatography techniques are described for the detection of methylmalonic acid in urine. 2. The separation of methylmalonic acid from a crude urine sample is performed by thin-layer chromatography with a mixture of silica gel-cellulose and butanol - acetic acid - water solvent system. The methylmalonic acid spot is visualized with tetrazotized o-dianisidine. 3. This system has been successfully developed for a urinary screening programme; it was shown as simple, convenient and rapid, eliminating false-positives and allowing the detection of even traces of methylmalonic acid.

Chromatography, Thin Layer↗
PubMed1992

Serum methylmalonic acid before and after oral L-isoleucine loading in cobalamin-deficient patients.

Over a 1 1/2-year period, we measured concentrations of methylmalonic acid in serum before and after a standardized loading with oral L-isoleucine (100 mmol) in 13 patients admitted for evaluation of cobalamin deficiency. All patients had serum cobalamin values below 100 pmol l-1, but only 12 of the 13 patients were clinically confirmed cobalamin deficient. The clinically non-cobalamin-deficient patient had folate deficiency and was excluded. The serum methylmalonic acid concentrations before loading with isoleucine were above the upper reference limit (0.37 mumol l-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 mumol l-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 mumol l-1. The results show that a significant increase of an initially elevated serum methylmalonic acid concentration after isoleucine loading is a general finding in tissue cobalamin deficiency which strongly supports the diagnosis.

Administration, Oral↗
PubMed1975

A simplified and rapid quantitative assay for propionic and methylmalonic acids in urine.

Propionic and methylmalonic aciduria occur individually in inborn errors of metabolism and together in vitamin B12-deficient states. A method is described for the simultaneous and rapid extraction of these acids from urine and their quantification by a simple gas chromatographic technique. The assay is based upon the spontaneous and quantitative decarboxylation of methylmalonic acid (MMA) at 225 degrees C. to its monocarboxylic acid product, propionic acid. By utilizing another substituted malonic acid, ethylmalonic acid, as a specific internal standard, accurate quantitation is possible by peak height ratio analysis, Endogenous propionic acid is then measured at 130 degrees C., a temperature at which methylmalonic acid does not decarboxylate. The assay is rapid with a total running time of approximately 2 hours. The method provides excellent resolution of propionic acid excretion at or above 0.5 mg. per liter of urine. The level of resolution for methylmalonic acid, in the presence of propionic aciduria, was 5 mg. per liter of urine.

Chromatography, Gas↗
PubMedDate not supplied

[Methylmalonic acid excretion in experimental B2-avitaminosis in rats].

Providing of rats with a diet, deficient in vitamin B2 within 2 and 5 weeks, was not shown to be accompanied by an increase in excretion of methylmalonic acid. In the animals some tendency to the increased excretion of methylmalonic acid was observed within 8 weeks of the diet. The data obtained suggest that the test for excretion of methylmalonic acid was the highly specific as a pattern of supply with vitamin B12. The possible role of vitamin B2 and flavoproteins in biosynthesis of coenzyme forms of vitamin B12 is discussed.

Animals↗
PubMed1979

Colorimetric method for determination of urinary methylmalonic acid.

The colorimetric method for the determination of methylmalonic acid by coupling with diazotised p-nitroaniline has been re-examined. Extraction of the diazotised product into amyl alcohol and tetra-methyl ammonium hydroxide considerably increases its stability and sensitivity and reduces background absorbance. Preliminary solvent extraction and ion-exchange chromatography are desirable but can be accomplished simply and quickly using very small quantities of urine. In this form, the method is very reliable and gives recoveries of about 95% and a coefficient of variation of about 7%.

Colorimetry↗
PubMed1979

Methylmalonic acid metabolism of germfree and conventional vitamin B-12 deprived rats fed precursors of methylmalonate.

Experiments using germfree (GF), ex-germfree (XGF) and conventional (CONV) rats were conducted to study the relationship of intestinal microorganisms to vitamin B-12 (B-12) status and to methylmalonic acid (MMA) excretion of the host animal, since B-12 depleted GF rats have been found to excrete less than expected level of urinary MMA. The possibility that the GF rat lacks sufficient precursor of MMA was tested by feeding GF, XGF and CONY rats diets low or high in MMA precursors and examining urinary excretion of MMA and formiminoglutamic acid at intervals. The possibility that the GF rat may metabolize propionate and MMA differently from the CONV rat was examined by a MMA loading-recovery study and a CO2 collection study after [14C]propionate injection. Plasma and tissue B-12 levels were determined at the beginning and the end of the study. Results indicate that 1) lack of sufficient precursor of MMA is partly responsible for the failure of GF, B-12 deficient rat to excrete MMA, 2) GF and CONV rats metabolize propionate and MMA by the same pathways and 3) the presence of intestinal microorganism depletes the body B-12 store of the rat.

Animals↗
PubMed1975

[13C]Valine metabolism in methylmalonicacidemia using nuclear magnetic resonance: propinonate as an obligate intermediate.

[Alpha-13C]- and [alpha,beta-13C]valine were administered sequentially to a patient with methylmalonicacidemia to clarify the metabolic pathway of valine from methylmalonic acid semialdehyde to methylmalonyl-CoA. Methylmalonic acid was isolated from multiple urine samples, purified, and analyzed by 13C nuclear magnetic resonance spectroscopy. Contrary to the widely accepted view, the results show unequivocally that methylmalonic acid semialdehyde is decarboxylated to propionate before conversion to methylmalonyl CoA.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

High prevalence of cobalamin deficiency in elderly outpatients.

OBJECTIVE: To measure the prevalence of cobalamin (vitamin B12) deficiency in geriatric outpatients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment. DESIGN: Prospective study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays. In patients with serum cobalamin levels < or = 300 pg/mL, the response to cobalamin treatment in the group with levels of methylmalonic acid and/or homocysteine > 3 standard deviations (SD) above the mean for normals was compared with that of those without such elevations. SETTING: Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center, Denver, CO. PATIENTS: One-hundred and fifty-two consecutive outpatients, ages 65 to 99, were screened. Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospectively evaluated and treated with cobalamin. MAIN OUTCOME MEASURES: Cobalamin, methylmalonic acid, homocysteine, complete blood counts, neurologic examination, and neuropsychological testing. RESULTS: The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and/or homocysteine elevated to > 3 SD was 14.5% of the screened outpatients. A similar proportion of patients with low normal serum cobalamin levels (between 201 and 300 pg/mL) demonstrated elevated metabolites > 3 SD (56%) compared with patients with low serum cobalamin levels (< or = 200 pg/mL) (62%). Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospectively. Results for complete blood count, lactate dehydrogenase, bilirubin, baseline neurologic score, and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites. The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment. One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment. CONCLUSION: There was a high (14.5%) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly outpatients. The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201-300 pg/mL compared with patients with low cobalamin levels (< or = 200 pg/mL) had markedly elevated metabolites which fell with cobalamin treatment. Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects.

Aged↗
PubMed1979

Megaloblastic anemia as a result of an abnormal transcobalamin II (Cardeza).

A 34-year-old Black woman had severe megaloblastic anemia in childhood. Initially, and over the years, she responded well to massive doses of parenteral cobalamin (Cbl) or oral folic acid. Metabolic reactions involving Cbl and folate enzymes were normal during both relapse and remission except for the absence of thymidylate synthetase in relapse. Amino acid analyses of urine and plasma showed no significant abnormalities. Neither cystathionine, homocystine, formiminoglutamic acid, nor methylmalonic acid was detected in the urine. The serum Cbl level was repeatedly elevated even when the patient was receiving only folic acid therapy. The elevation of the vitamin in the serum was found to be a result of markedly increased levels of transcobalamin II (TC II), as identified by several physicochemical techniques. The patient's TC II-Cbl shared immunologic properties with normal TC II but did not facilitate or impede the uptake of Cbl or Cbl bound to normal TC II, respectively, by human cells.

Anemia, Macrocytic↗
PubMed1979

Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy.

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.

Amino Acid Metabolism, Inborn Errors↗