Unit Converter
Homocysteine (HCY)
(Sulfur-Containing Amino Acid – Marker for Cardiovascular Risk, B-Vitamin Deficiency & Inborn Metabolic Disorders)
Synonyms
- Homocysteine
- Total homocysteine (tHCY)
- Plasma homocysteine
- HCY
- Hyperhomocysteinemia marker
Units of Measurement
- µmol/L
- mg/dL
- mg/100 mL
- mg%
- mg/L
- µg/mL
Key Conversions
(Molecular Weight ≈ 135.18 g/mol)
1 mg/L = 7.40 µmol/L
1 mg/dL = 74.0 µmol/L
1 µg/mL = 1 mg/L
mg/100 mL = mg/dL = mg%
1 µmol/L = 0.135 mg/L
Description
Homocysteine is a non-protein sulfur-containing amino acid derived from methionine metabolism.
Homocysteine is:
- Remethylated to methionine (requires vitamin B12 + folate)
- Converted to cystathionine (requires vitamin B6)
Disruption of these pathways raises homocysteine.
Elevated homocysteine is an important marker for:
- Cardiovascular risk
- Vitamin B12/B6/folate deficiency
- Inborn errors of metabolism
- Kidney dysfunction
Physiological Role
Although not incorporated into proteins, homocysteine is central to:
1. Methylation Pathways
Remethylation cycle → SAM (S-adenosylmethionine) production, essential for:
- DNA methylation
- Neurotransmitter synthesis
- Cellular repair
2. Transsulfuration Pathway
Produces cysteine → glutathione → antioxidant defense.
3. Vascular Function (Pathological)
High homocysteine:
- Injures endothelium
- Promotes oxidative stress
- Enhances thrombosis
- Accelerates atherosclerosis
Clinical Significance
High Homocysteine (Hyperhomocysteinemia)
(Most important clinically)
1. Cardiovascular & Thrombotic Risk
Associated with:
- Coronary artery disease
- Stroke
- Peripheral vascular disease
- Venous thrombosis
Mechanisms:
- Endothelial dysfunction
- Oxidative stress
- Prothrombotic effects
2. Vitamin Deficiencies
- Vitamin B12 deficiency
- Folate deficiency
- Vitamin B6 deficiency
Most common cause of elevated HCY in practice.
3. Renal Insufficiency
Homocysteine clearance ↓ → accumulation.
4. Hypothyroidism
Reduced metabolism → mild elevation.
5. Medications
- Methotrexate
- Metformin
- Anti-epileptics (phenytoin, carbamazepine)
- Theophylline
6. Inborn Errors of Metabolism
Homocystinuria (CBS deficiency) → very high homocysteine.
Clinical features:
- Marfanoid habitus
- Lens dislocation
- Thrombosis
- Developmental delay
Levels usually >100–200 µmol/L.
7. Smoking & Alcohol
Increase oxidative stress → mild elevations.
Low Homocysteine
Rare, and usually not clinically significant.
Occasionally seen in:
- Excess vitamin supplementation (B12, B6, folate)
- Pregnancy
- Cystathionine beta-synthase overactivity (rare)
Reference Intervals
(Tietz 8E + Mayo + ARUP + AHA/ACC)
Adults
- Normal: <15 µmol/L
- Mild elevation: 15–30 µmol/L
- Moderate: 31–100 µmol/L
- Severe: >100 µmol/L (suggests homocystinuria)
Children
- Typically lower: 5–10 µmol/L
Pregnancy
Levels fall to 4–12 µmol/L.
Diagnostic Uses
1. Cardiovascular Risk Assessment
- Adjunct marker (especially in premature CVD, unexplained thrombosis)
2. Screening for Vitamin Deficiencies
Sensitive marker for:
- B12 deficiency
- Folate deficiency
- B6 deficiency
Often paired with:
- Methylmalonic acid (MMA)
- B12 / folate levels
3. Inborn Error Diagnosis (Homocystinuria)
Very high levels → pathognomonic.
4. Monitoring Therapy
- Vitamin supplementation
- Dietary methionine restriction (homocystinuria)
5. Renal & Thyroid Disorders
HCY helps assess metabolic impact.
Analytical Notes
- Fasting plasma preferred
- Blood must be kept on ice and separated quickly (RBCs generate homocysteine)
- EDTA plasma most reliable
- Stable for days when frozen
- Measured using immunoassay, HPLC, or LC/MS
Clinical Pearls
- The most common cause of elevated homocysteine is B12 or folate deficiency, not genetics.
- Normal MMA + high homocysteine → think folate deficiency.
- High MMA + high homocysteine → B12 deficiency.
- Homocystinuria patients have very high levels (>100 µmol/L) and high thrombotic risk.
- Elevated homocysteine is a modifiable cardiovascular risk factor.
Interesting Fact
Homocysteine was discovered in 1932, but its connection to atherosclerosis was made by Kilmer McCully in the 1960s-leading to the “homocysteine theory” of vascular disease.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Amino Acids & Homocysteine.
- AHA/ACC Guidelines - Cardiovascular Risk Markers.
- ACMG Guidelines - Homocystinuria Diagnosis.
- Mayo Clinic Laboratories - Homocysteine.
- ARUP Consult - Hyperhomocysteinemia Workup.
- NIH / MedlinePlus - Homocysteine Testing.