Homocysteine

Plasma and urine homocysteine tests are indicated in the screening and diagnosis of different types of homocystinuria.

Normal findings: 4-14 μmol/L (Levels may rise with age.) ^[1]

Plasma and urine homocysteine levels are usually elevated in homocystinuria, an inborn error of metabolism that can result from many enzymatic defects, including the following:

• Cystathionine β-synthase deficiency

• Defects in methylcobalamin formation ^[2]

• Methylenetetrahydrofolate reductase deficiency

Plasma homocysteine levels are elevated in vitamin B-12 deficiency, vitamin B-6 deficiency and in folic acid deficiency. ^[3]

Whether elevated plasma and urine homocysteine levels represent a cardiovascular risk factor is debatable. ^[4]

Plasma homocysteine levels can also increase in association with increading age, hypothyroidism, impaired kidney function, systemic lupus erythematosus, and certain medications, such as nitrous oxide, methotrexate, phenytoin, and carbamazepine.

Patient instructions: Fasting is preferred

Collection tube: Lavender-top tube, green-top tube, or gel-barrier tube

Unacceptable conditions: Grossly hemolyzed specimens

Specimen preparation: Plasma (preferred) or serum should be separated within one hour of collection and then transferred to a transport tube.

Storage/transport temperature: Refrigerated

Stability: Room temperature, 1 hour; refrigerated, 1 week; frozen, 3 months

Panels: None

Description

Homocysteine is a sulfur-containing amino acid; in plasma, it undergoes oxidization and transforms to disulfides homocystine and cysteine-homocysteine, the measured plasma level reflects these 3 components.

Homocysteine play an important role in many metabolic pathways, mainly the methionine cycle to the folate cycle (see image below). ^[5]

Caption: Homocysteine involvement in different metabolic pathways, as well as the role of vitamin B-6, vitamin B-12, and folate as cofactors in these pathways.

Indications/Applications

Plasma and urine homocysteine tests are indicated in the screening and diagnosis of different types of homocystinuria.

Considerations

Plasma homocysteine levels are usually severely elevated in homozygous cystathionine-β synthase deficiency and moderately elevated in heterozygous cystathionine-β synthase deficiency. In the other mutations associated with homocystinuria, plasma levels can vary from high to intermediate.

Many epidemiological studies have shown that plasma homocysteine levels are higher in patients with coronary heart disease, stroke, peripheral vascular disease, or thromboembolic disease, but recent meta-analysis showed that lifelong moderate homocysteine elevation has little or no effect on coronary heart disease. ^{[6, 4]}

Plasma homocysteine levels can be elevated in vitamin B-12, folate (vitamin B-9), and vitamin B-6 deficiencies.

In most cases, vitamin B-12 deficiency is associated with an elevation in plasma homocysteine and methylmalonic acid levels, whereas folate deficiency is associated with elevated homocysteine levels only.