Folate deficiency tests

Rule out vitamin B]2 and folate deficiency Rule out hypothyroidism with thyroid function tests Blood cell counts, serum electrolytes, liver function tests Other diagnostic tests... 

Management is essentially the same as for folate deficiency but the site of the lesion, that may necessitate further investigation and treatment, needs accurate definition by means of the Schilling test. Additional useful determinations are homocysteine and methylmalonic acid levels. 

METHOTREXATE ANTIMALARIALS -PYRIMETHAMINE t antifolate effect of methotrexate Pyrimethamine should not be used alone and is combined with sulfadoxine. Pyrimethamine and methotrexate synergistically induce folate deficiency Although the toxic effects of methotrexate are more frequent with high doses of methotrexate, it is necessary to do an FBC, liver and renal function tests before starting treatment even with low doses, repeating these tests weekly until therapy is stabilized and thereafter every 2-3 months. Patients should be advised to report symptoms such as sore throat and fever immediately, and also any gastrointestinal discomfort. A profound drop in white cell count or platelet count warrants immediate stoppage of methotrexate therapy and initiation of supportive therapy... 

Abnormal response to a metabolic load, such as the inability to metabolize a test dose of histidine in folate deficiency (Section 10.10.4), or tryptophan in vitamin Be deficiency (Section 9.5.4), although at normal levels of intake there may be no metabolic impairment. 

The ability to metabolize a test dose of histidine provides a sensitive functional test of folate nutritional status as shown in Figure 10.6, forrnirninoglu-tamate (FIGLU) is an intermediate in histidine catabolism and is metabolized by the tetrahydrofolate-dependent enzyme FIGLU forrnirninotransferase. In folate deficiency, the activity of this enzyme is impaired, and FIGLU accumulates and is excreted in the urine, especially after a test dose of histidine - the FIGLU test. 

In experimental animals and with isolated tissue preparations and organ cultures, the test can be refined by measuring the production of G02 from [ C]histidine in the presence and absence of added methionine. If the impairment of histidine metabolism is the result of primary folate deficiency, the addition of methionine wUl have no effect. By contrast, if the problem is trapping of folate as methyl-tetrahydrofolate, the addition of methionine will restore normal histidine oxidation as a result of restoring the inhibition of methylene-tetrahydrofolate reductase by S-adenosylmethionine and restoring the activity of 10-formyl-tetrahydrofolate dehydrogenase, thus permitting more normal folate metabolism (Section 10.3.4.1). 

Indirect tests assess the functional adequacy of vitamin Bi2. Serum methylmalonic acid concentration is increased when a lack of adenyl-Cbl causes a block in the conversion of methylmalonyl-CoA to succinyl-CoA. It is a sensitive test of status, being often the first analyte to be raised in sub-clinical vitamin B12 deficiency. It has a further advantage in that it is unaffected by folate deficiency. Early methods for methylmalonic acid lacked sensitivity and specificity, a situation that has been resolved by the adoption of gas chromatographic-mass spectrometric methods,though these require specialized handling. Plasma total homocysteine concentration is a sensitive indicator of vitamin B status, because methyl-Cbl is required for the remethylation of... 

Folate deficiency leads to accumulation of Figlu, which is excreted in urine. The excretion is very pronounced after a loading dose of histidine, a test used to detect folate deficiency. More sensitive radioisotopic assays use folate binders to the vitamins. High urinary levels of Figlu may coexist with elevated levels of serum folate. Thus, in vitamin Bn (cobalamin) deficiency, since cobalamin participates in the following reaction, FH4 is trapped as... 

A deficiency of folate results in the accumulation of FIGLU, which is excreted in the urine. A histidine load test can be used for detecting folate deficiencies. Patients were given a test dose of histidine (a histidine load), and the amount of FIGLU that appeared in the urine was measured. 

An in vivo test for the investigation of suspected folic acid deficiency. The normal metabolism of histidine contains a step in which formiminoglutamic acid (FIGLU) is converted to glutamate by an enzyme which uses folate as a cofactor. In patients with folate deficiency, administration of oral histidine results in a greater than normal urinary excretion of FIGLU. 

Folate administration three days prior to immunization raised the level to 30/10. Decreased complement-fixation titers have also been observed by Wertman et al. (1952) in folate deficient rats. In an attempt to produce antibodies against the hapten p-aminobenzoylglutamate diazotized to bovine serum albumin, Rothenberg et al. (1973) found that antibody production was markedly depressed in folate-deficient mice and remained so many months following folate repletion even with repeated immunizing injections. Three months following supplementation there was a normal antibody response to SRBC injection but this parameter was never tested on the deficient animals. 

PHA (Stimulation index 14.8 in controls compared to 3.0 in folate deficient). An in vivo measurement of cell-mediated immune function (skin test sensitivity to intradermal PHA injection) showed a depressed response in the deficient animals based on the degree of mononuclear cell infiltration. 

Most research on the effect of folate deficiency on lymphoid cell metabolism has focused on the enzymes involved in pyrimidine synthesis. Defective interconversion of glycine and serine has been reported in peripheral lymphocytes from folate deficient patients due to folate malabsorption, malnutrition or treatment with phenytoin (Ellegaard and Esmann, 1972), methotrexate, (Ellegaard and Esmann, 1973). In fact estimation of serine formation in lymphocytes cultured with glycine and labeled formate is the basis for the test developed to detect early folate deficiency before the appearance of megaloblastic changes in the bone marrow and low RBC folate levels (Ellegaard and Esmann, 1973). 

The dU suppression test is now regarded as a diagnostic tool to distinguish marked or subclinical megaloblastic anemia and to identify the underlying nutritional defect. Similar results have been observed in PHA-stimulated peripheral l5nnphocytes from patients with untreated pernicious anemia or folate deficient megaloblastic anemia. 

Unmasking covert folate deficiency in iron-deficient subjects with neutrophil hypersegmentation dU suppression tests on l3nnphocytes and bone marrow, B. J. Haematol.,... 

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