6 Metabolite assays in cobalamin and folate deficiency

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Cbl and folate are both necessary for the metabolism of HCYS, whereas only Cbl is required for MMA metabolism. During the past decade, analytical methods have been developed that are sensitive enough to detect low levels of MMA and HCYS normally present in the plasma. These methods are sufficiently precise to be used in the clinical laboratory and measurements of the serum levels of the metabolites provide sensitive and specific techniques for the identification of Cbl and folate deficiencies. These techniques constitute an important addition to the battery of diagnostic tests that are available for detecting the vitamin deficiencies and for distinguishing each from the other. By virtue of the role of Cbl and folate in the metabolic pathways that involve MMA and HCYS, levels of both metabolites rise in Cbl deficiency, but only HCYS rises in folate deficiency. During the development of Cbl or folate deficiencies, accumulation of these metabolites in the plasma signals the existence of a condition of biochemical vitamin deficiency of sufficient degree to cause impairment in the metabolic pathways which are dependent on these vitamins. Circulating metabolite levels appear to accurately reflect the nutritional status of the vitamins and a rise in serum metabolite levels is therefore one of the earliest and most reliable indicators of developing Cbl and folate deficiencies. Elevations of serum metabolites above the reference range not only precede a fall in the serum vitamin levels but also show a more consistent correlation with objective evidence of vitamin deficiency than do low blood vitamin levels. The advent of serum metabolite measurements has also made it possible to identify subtle or atypical forms of vitamin deficiency that may be associated with unusual or previously undiscovered disease manifestations. Thus, in patients who display only neurological manifestations of disease, underlying Cbl deficiency may be revealed by the finding of raised serum or urine levels of MMA. Similarly, unsuspected folate deficiency may be disclosed by the finding of a raised serum HCYS. This may have important implications with respect to disease risk, since there is mounting evidence that sub-optimal folate nutritional status may be associated with increased risks of vascular disease, neoplasia and birth defects. Finally, the measurement of serum levels of MMA, HCYS and other metabolites that accumulate in Cbl and folate deficiencies may provide important new insights into the mechanism whereby these vitamin deficiencies lead to different patterns and manifestations of disease.

Original languageEnglish (US)
Pages (from-to)533-566
Number of pages34
JournalBailliere's Clinical Haematology
Volume8
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Vitamin B 12
Folic Acid
Avitaminosis
Serum
Vitamins
Metabolic Networks and Pathways
Nutritional Status
Neurologic Manifestations
Vascular Diseases
Routine Diagnostic Tests
Reference Values
Urine

ASJC Scopus subject areas

  • Hematology

Cite this

6 Metabolite assays in cobalamin and folate deficiency. / Green, Ralph.

In: Bailliere's Clinical Haematology, Vol. 8, No. 3, 1995, p. 533-566.

Research output: Contribution to journalArticle

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