Anemia Profile, Megaloblastic

Serum or plasma

2 mL

1 mL

Red-top tube, gel-barrier tube, or green-top (heparin) tube

Diagnose megaloblastic anemia. Elevated levels of methylmalonic acid provide an early indication of cobalamin (B₁₂) deficiency.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

Serum methylmalonic acid and homocysteine are the primary metabolic tests for diagnosing and distinguishing between B₁₂ and folate deficiency. They can be used in conjunction with the serum B₁₂, which is usually low or low normal (<350 pg/mL) in B₁₂ deficiency, and the serum folate, which is usually low or low normal (<5 ng/mL) in folate deficiency. 2-Methylcitric acid and cystathionine provide confirmatory evidence for such deficiencies. Homocysteine, and especially cystathionine, may also be high in B₆ deficiency.

Elevated levels of serum metabolites will correct to normal after treatment with the appropriate vitamin but will not correct after treatment with the wrong vitamin, even in pharmacologic amounts.

Any of the four metabolites can be elevated due to renal insufficiency or intravascular volume depletion. This occurs most commonly in the case of 2-methylcitric acid and cystathionine. Elevated metabolite levels do not correct with B₁₂, folate, or B₆ treatment, unless vitamin deficiency coexists.

Normal ranges six hours postoral methionine load (100 mg L-methionine/kg body weight) are as follows: homocysteine: 16.5−45.7 μmol/L and cystathionine: 424−2500 nmol/L. Methylmalonic acid and 2-methylcitric acid do not change after a methionine load.

The megaloblastic anemia profile monitors four compounds: methylmalonic acid, 2-methylcitric acid, homocysteine, and cystathionine. It has been shown that all four of these compounds are elevated if a patient is suffering from vitamin B₁₂ deficiency (megaloblastic anemia, cobalamin deficiency) and that homocysteine and cystathionine are elevated if there is a folic acid deficiency. Methylmalonic acid and homocysteine are the primary tests for diagnosis. 2-Methylcitric acid and cystathionine provide confirmatory information.

This method is a more specific diagnostic tool for B₁₂ and folate deficiencies as it has been shown that some patients with deficiencies will have normal or borderline serum B₁₂ or folate. A deficiency of vitamin B₁₂ can lead to incapacitating and life-threatening neuropsychiatric abnormalities, which are completely reversible by treatment with B₁₂. As with any such condition early detection is very important. This profile provides early detection and differentiation. This differentiation is very important because both B₁₂ and folate deficiencies have indistinguishable hematological abnormalities. The greatest improvement is observed when the proper vitamin is used and only B₁₂ will correct the neuropsychiatric abnormalities seen in cobalamin deficiency.