Test Code

Alias/See Also
Megaloblastic Anemia Panel

Preferred Specimen

Minimum Volume
1.0 mL

Separate serum or plasma from cells within one hour of collection and transfer to plastic transport tube.

Transport Container

Specimen Stability

Setup Schedule
Set Up:
Report Available:2-3 WEEKS

Clinical Significance

Diagnose megaloblastic anemia. Elevated levels of methylmalonic acid provide an early indication of cobalamin (B(12)) deficiency. 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 B(12) 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 B(12) and folate deficiencies as it has been shown that some patients with deficiencies will have normal or borderline serum B(12) or folate. A deficiency of vitamin B(12) can lead to incapacitating and life-threatening neuropsychiatric abnormalities, which are completely reversible by treatment with B(12). As with any such condition early detection is very important. This profile provides early detection and differentiation. This differentiation is very important because both B(12) and folate deficiencies have indistinguishable hematological abnormalities. The greatest improvement is observed when the proper vitamin is used and only B(12) will correct the neuropsychiatric abnormalities seen in cobalamin deficiency. The reference range for methylmalonic acid has been set at +3 SD above the mean for healthy blood bank donors. In the clinical assessment of patients with megaloblastic anemias, a cutoff of +3 SD provides greater specificity in the diagnosis of the vitamin deficiency states, despite the sacrifice of some sensitivity. 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. Serum metabolite levels can be rechecked 5 to 15 days after vitamin therapy. Normal ranges six hours postoral methionine load (100 mg L-methionine/kg body weight) are as follows: homocysteine: 16.5-45.7 umol/L and cystathionine: 424-2500 nmol/L. Methylmalonic acid and 2-methylcitric acid do not change after a methionine load.  

Performing Laboratory

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.