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

@article{Allen1990DiagnosisOC,
  title={Diagnosis of cobalamin deficiency I: Usefulness of serum methylmalonic acid and total homocysteine concentrations},
  author={Robert H. Allen and Sally P. Stabler and David G. Savage and John Lindenbaum},
  journal={American Journal of Hematology},
  year={1990},
  volume={34}
}
The serum cobalamin assay is the primary diagnostic test for cobalamin deficiency. It appears to be an excellent screening test since most patients with clinically confirmed cobalamin deficiency have low levels. Recent studies indicate that the clinical picture of cobalamin deficiency is much more diverse than previously believed. It is also apparent that many patients with low serum cobalamin concentrations are not cobalamin deficient. Thus, there is a need for additional diagnostic tests to… 

Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations

It is concluded that the serum cobalamin is normal in a significant minority of patients with cobalamine deficiency and that the measurement of serum metabolite concentrations facilitates the identification of such patients.

How to diagnose cobalamin deficiency.

It is suggested that either assay of P--cobalamins or P--methylmalonate is employed as screening test for cobalamin deficiency, and that further tests are performed only if the initial test in combination with the clinical picture gives an unclear answer.

Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin

Abstract: We prospectively studied 41 consecutive elderly patients with serum cobalamin (vitamin B12) levels lower than 125 pmol/l. The protein‐bound cobalamin absorption test (PBAT) was performed in

Methylmalonic acid in serum from patients with neurological symptoms consistent with cobalamin deficiency

Test if serum‐methylmalonic acid (S‐MMA) can identify patients with neurological symptoms due to cobalamin deficiency in spite of a normal plasma cobalamine level and found a significant decrease in S‐Mma below 0.37 μmol/l was found in 11 patients treated, indicating a functional cobalamina deficiency.

Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms

The use of holoTC in the present study group did not give significant additional information other than that given by serum cobalamin and therefore cannot be recommended in this clinical setting.

Prevalence of cobalamin deficiency in the Framingham elderly population.

The prevalence of cobalamin deficiency was > or = 12% in a large sample of free-living elderly Americans, and metabolites correlated best with serum cobalamina values, even when subnormal determinations were excluded.

Metabolic cobalamin deficiency in patients with low to low-normal plasma cobalamins.

It is concluded that P-cobalamins below the reference interval combined with typical neuropsychiatric symptoms or findings are not diagnostic of cobalamin deficiency and that further analyses are necessary.

Plasma homocysteine in relation to serum cobalamin and blood folate in a psychogeriatric population

The findings in this study support the view that, in elderly patients with co‐existing organic brain disease, cobalamin substitution should be started when serumcobalamin concentrations are below 200 pmol l‐1 and plasma homocysteine is elevated, to prevent further organic lesions related to cobalamine deficiency.
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References

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Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations

It is concluded that the serum cobalamin is normal in a significant minority of patients with cobalamine deficiency and that the measurement of serum metabolite concentrations facilitates the identification of such patients.

Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry.

Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of total homocysteine while they were free of hematologic and neurologic abnormalities.

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

With rapid, reliable quantitation by mass spectrometry, urinary MMA can now be a useful clinical test in patients suffering from megaloblastic anemia, other anemias, elevated red cell mean corpuscular volume, or unexplained neurologic disorders.

Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry.

The ability to measure methylmalonic acid in human serum will be useful in studies designed to determine the incidence of cobalamin deficiency in various patient populations.

Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels.

The egg-yolk cobalamin absorption test was used to study 47 patients selected not because of known gastric disorders but because they had low serum cobalamine levels with normal Schilling test results, which found the finding of food cobalamina malabsorption in 60% of tested patients who had neurologic, cerebral, or psychiatric abnormalities.

Cobalamin analogues are present in human plasma and can mask cobalamin deficiency because current radioisotope dilution assays are not specific for true cobalamin.

Comparison of serum cobalamin values obtained with R protein and intrinsic factor in radioisotope dilution assays showed that the differences were due to the presence of cobalamine analogues.

Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking.

  • R. Carmel
  • Medicine
    Archives of internal medicine
  • 1988
It is shown that only 45 (64%) of 70 consecutively diagnosed patients with pernicious anemia had very low cobalamin levels (less than 74 pmol/L [or less than 100 ng/L], and macrocytosis was absent in 23 (33%) of the patients; such absence was particularly common when cobalamina levels were only slightly or moderately low.

The total serum homocysteine as an indicator of vitamin B12 and folate status.

  • R. ChuC. Hall
  • Medicine, Biology
    American journal of clinical pathology
  • 1988
The total serum Hcy was increased in vitamin B 12 and folate deficiency, and the level was high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B11 levels, but was normal in the absence of tissue deficiency even if the serumitamin B12 levels were low.

Evidence that some patients with pernicious anemia are not recognized by radiodilution assay for cobalamin in serum.

The development of radiodilution assays for measuring the serum cobalamin level has met the need for a rapid and simple method and has made this determination generally available.

Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.

It is concluded that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.