Anemia Profile, Megaloblastic

CPT: 82136; 83918
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Test Details

Synonyms

  • Megaloblastic Anemia

Test Includes

Cystathionine; homocysteine; 2-methylcitric acid; methylmalonic acid

Use

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

Methodology

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

Reference Interval

See table.

Anemia Profile, Megaloblastic, Serum

Serum Metabolite

Normal Range

% High Values

B12 Deficiency Range

% High Values

Folate Deficiency Range

% High Values

Methylmalonic acid

0−378

<1

379−200,000

>95

0−378 nmol/L

<1

2-Methylcitric acid

60−228

<3

228−15,000

>80

60−228 nmol/L

<3

Homocysteine

5.1−13.9

<3

14−500

>95

14−250 μmol/L

>95

Cystathionine

44−342

<3

342−4000

>80

342−18,000 nmol/L

>80

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 μmol/L and cystathionine: 424−2500 nmol/L. Methylmalonic acid and 2-methylcitric acid do not change after a methionine load.

Additional Information

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.

Specimen Requirements

Specimen

Serum or plasma

Volume

2 mL

Minimum Volume

1 mL

Container

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

Collection

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

Storage Instructions

Room temperature

Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Specimen received not separated from cells; plasma from a blue-top or yellow-top tube; citrate interferes with assay; homocysteine results increase by approximately 35% and 75% for specimens not centrifuged and/or not separated from the clot for periods of four and 24 hours respectively

Clinical Information

References

Lindebaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988 Jun 30; 318(26):1720-1728. 3374544
Marcell PD, Stabler SP, Podell ER, Allen RH. Quantitation of methylmalonic acid and other dicarboxylic acids in normal serum and urine using capillary gas chromatography-mass spectrometry. Anal Biochem. 1985 Oct; 150(1):58-66. 4083484
Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest. 1988 Feb; 81(2):466-474. 3339129

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
706960 Anemia, Megaloblastic, Serum 706797 Methylmalonic Acid, Serum nmol/L 13964-2
706960 Anemia, Megaloblastic, Serum 706962 2-Methylcitric Acid, Serum nmol/L 12540-1
706960 Anemia, Megaloblastic, Serum 706963 Homocysteine, Serum umol/L 13965-9
706960 Anemia, Megaloblastic, Serum 706967 Cystathionine, Serum nmol/L 26607-2
706960 Anemia, Megaloblastic, Serum 706976 Reference Ranges: N/A
706960 Anemia, Megaloblastic, Serum 706969 Continued: N/A
Reflex Table for Continued:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 700480 Disclaimer: 700480 Disclaimer: N/A

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