Homocysteine, Total, Plasma (HCYSP)

Test Code: HCYSPSO

Overview
Ordering
Specimen
Performing
Clinical/Interpretive
Contacts
Coding

Synonyms/Keywords

Cystathionine beta-synthase deficiency, Methylenetetrahydrofolate reductase deficiency (MTHFR), MTHFR deficiency, Methionine synthase deficiency, Cobalamin (Cbl) metabolism, Methyl-Cobalamin deficiency, Adenosyl-cobalamin deficiency, Cbl C2 deficiency, Cbl D2 deficiency, Cbl F3 deficiency, Cbl D-Var1 deficiency, Cbl E deficiency, Cbl G deficiency, Transcobalamin II deficiency, Adenosylhomocysteinase (AHCY) deficiency, Glycine N-methyltransferase (GNMT) deficiency, Methionine adenosyltransferase (MAT) I/III deficiency, Cobalamin C2 deficiencyCobalamin D2 deficiency, Cobalamin F3 deficiency, Cobalamin D-Variant 1 deficiency, Cobalamin E deficiency, Cobalamin G deficiency

Useful For

An aid for screening patients suspected of having an inherited disorder of methionine metabolism including:
-Cystathionine beta-synthase deficiency (homocystinuria)
-Methylenetetrahydrofolate reductase deficiency (MTHFR) and its thermolabile variants
-Methionine synthase deficiency
-Cobalamin (Cbl) metabolism
-Combined methyl-Cbl and adenosyl-Cbl deficiencies: Cbl C2, Cbl D2, and Cbl F3 deficiencies
-Methyl-Cbl specific deficiencies: Cbl D-Var1, Cbl E, and Cbl G deficiencies
-Transcobalamin II deficiency
-Adenosylhomocysteinase (AHCY) deficiency
-Glycine N-methyltransferase (GNMT) deficiency
-Methionine adenosyltransferase (MAT) I/III deficiency
-Screening and monitoring patients suspected of or confirmed with an inherited disorder of methionine metabolism
-Evaluating individuals with suspected deficiency of vitamin B12 or folate.

Specimen Requirements

Fasting Required	Specimen Type	Preferred Container/Tube	Acceptable Container/Tube	Specimen Volume	Specimen Minimum Volume (allows for 1 repeat)	Pediatric Minimum Volume (no repeat)
No	EDTA Plasma	Lavender Top Tube (LTT)	Green Top Tube (sodium or lithium heparin)	1.0 mL	0.10 mL	0.10 mL

Collection Processing Instructions

1. Patient's age and gender are required.

2. Immediately place specimen on wet ice.

3. Centrifuge and aliquot plasma into plastic vial within 4 hours of collection.

4. If blood cannot be placed on wet ice immediately, centrifuge and aliqout plasma into plastic vial within 1 hour of collection.

5. A refrigerated centrifuge is not required if the above time restrictions are met.

Specimen Stability Information

Specimen Type	Temperature	Time
Plasma EDTA	Refrigerate (preferred)	28 days
	Ambient	28 days
	Frozen	309 days

Rejection Criteria

Hemolysis	Gross
Lipemia	Gross
Icterus	Gross

Interference

Homocysteine concentration is affected by supplementation of vitamins B12, B6, or folate.

Factors that may influence and increase plasma homocysteine include:

-Age

-Smoking

-Poor diet/cofactor deficiencies

-Chronic kidney disease/renal disease

-Hypothyroidism

Medications that may increase homocysteine concentrations include:

Medication	Effect
Methotrexate	5-Methyltetrahydrofolate depletion
Azuridine	Vitamin B6 antagonist
Nitrous Oxide	Inactivation of methionine synthase
Phenytoin	Interference with folate metabolism
Carbamazepine	Interference with folate metabolism
Oral Contraceptives	Estrogen-induced vitamin B6 deficiency

Performing Laboratory Information

Performing Location	Day(s) Test Performed	Analytical Time	Methodology/Instrumentation
Mayo Clinic Laboratories	Monday through Friday	3-5 days	Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reference Lab

Mayo Clinic Laboratories

Test Information

Homocysteine is an intermediary in the sulfur-amino acid metabolism pathways, linking the methionine cycle to the folate cycle. Inborn errors of metabolism that lead to homocysteinemia or homocystinuria include cystathionine beta-synthase deficiency (homocystinuria) and various defects of methionine remethylation. Genetic defects in vitamin cofactors (vitamins B6, B12, and folate) and nutritional deficiency of vitamin B12 and folate also lead to abnormal homocysteine accumulation.

Homocysteine concentration is an indicator of acquired folate or cobalamin deficiency and is a contributing factor in the pathogenesis of neural tube defects. Homocysteine was also thought to be an independent predictor of cardiovascular disease (atherosclerosis, heart disease, thromboembolism), as early observational studies prior to the year 2000 linked homocysteine to cardiovascular risk and morbidity and mortality. However, following U.S. Food and Drug Administration mandated folic acid supplementation in 1998, homocysteine concentrations decreased by approximately 10% without a similar change in cardiovascular or ischemic events. Currently, the use of homocysteine for assessment of cardiovascular risk is uncertain and controversial. Based on several meta-analyses, at present, homocysteine may be regarded as a weak risk factor for coronary heart disease, and there is a lack of direct causal relationship between hyperhomocysteinemia and cardiovascular disease. It is most likely an indicator of poor lifestyle and diet.

This test should be used in conjunction with plasma amino acids, quantitative acylcarnitines, methylmalonic acid, and urine organic acids to aid in the biochemical screening for primary and secondary disorders of methionine metabolism.

Reference Range Information

See Report

Interpretation

Elevated homocysteine concentrations are considered informative in patients evaluated for suspected nutritional deficiencies (vitamin B12, foltate) and inborn errors of metabolism. Measurement of methylmalonic acid (MMA) distinguishes between B12 (cobalamin) and folate deficiencies, as MMA is only elevated in vitamin B12 deficiency. Treatment response can be evaluated by monitoring plasma homocysteine concentrations over time.

Outreach CPTs

CPT	Modifier (if needed)	Quantity	Description	Comments
83090		1	Homocysteine, Total, Plasma