Homocysteine

Homocysteine is formed during the breakdown of the essential amino acid methionine and is immediately converted further in healthy individuals, so that it is only present in small amounts in the body. In the context of hyperhomocysteinemia (synonym: homocysteinemia), the blood concentration of homocysteine (Hcy) is increased. Homocysteinemia causes damage to the endothelium (thin layer of endothelial cells lining the inside of blood vessels) and inactivation of protein C (→ thrombosis and thrombosis embolism risk↑). At the same time, there is activation of factor V (proaccelerin), which promotes blood clotting. Hyperhomocysteinemia can be, among other things, genetically determined. This is the case with a polymorphism of methylenetetrahydrofolate reductase (MTHFR): the mode of inheritance is autosomal recessive; point mutation; enzyme activity MTHFR is reduced by 35-90% in affected individuals:

  • “Wild type” – (normal, non-mutated gene variant = healthy); incidence: 40-50% in European-origin populations.
  • Heterozygous trait carrier; allele constellation: CT (35% restriction of folic acid metabolism); frequency: 45-47% (homocysteine levels of 11.9 ± 2.0 μmol/l)
  • Homozygous trait carrier; allele constellation: TT (80-90% restriction of folic acid metabolism); frequency: 12-15% (homocysteine levels of 14.4 ± 2.9 μmol/l)

Furthermore, genetic enzyme defects affecting cystathionine-β-synthase (CBS), cystathionine lyase (CL), homocysteine methyltransferase (HMT) or betaine homocysteine methyltransferase (BHMT) can have a sometimes serious effect on homocysteine levels. Moderate homocysteinemia (homocysteine levels > 30-100 µmol/l) and severe homocysteinemia (homocysteine levels > 100 µmol/l) develop.

The procedure

Material needed

  • Citrate-stabilizing EDTA plasma
  • Serum possible

Interfering factors

  • The decrease should be fasting, because methionine present in the diet leads to an increase in homocysteine concentration
  • Since homocysteine is synthesized by erythrocytes (red blood cells), the plasma must be stored separately from the blood cells as soon as possible.

Standard values

Standard values in µmol/l Therapeutic consequences
Favorable < 10 No action required
Tolerable (in healthy individuals) 10-12 Therapy necessary for patients at increased risk for atherosclerotic disease!For details, see hyperhomocysteinemia/other therapy below.

Indications (areas of application)

  • Thrombophilia diagnosis (looking for mutations in the MTHFR gene); patients with thromboembolic diseases.
  • Atherosclerosis risk stratification.
  • Suspected deficiency of folic acid, vitamin B6 or vitamin B12.
  • Diagnosis of homocysteinemia in the presence of vascular disease (myocardial infarction / heart attack, apoplexy / stroke, etc.).
  • Indicator of an acquired folate (folic acid) or vitamin B6 and B12 deficiency.
  • Suspected homocystinuria* – inborn error of metabolism.
  • Diagnosis of hyperhomocysteinemia pre-conceptional (before conception), that is, examination in the context of family planning/childbearing, since homocysteinemia is a risk factor for neural tube defects (spina bifida/open back), etc.

* Two molecules of homocysteine (Hcy) can combine via a disulfide bridge to form homocystine. With increased homocysteine levels in the blood (= homocsyteinemia) homocystine is excreted in the urine (homocystinuria).

Interpretation

Interpretation of elevated values

Forms of homocysteinemia Serum levels in µmol/l Therapeutic consequences
Mild homocysteinemia(mostly vital substance deficiency: B6, B12, folic acid). > 12-30 Therapy necessary for all (healthy individuals and patients)
Moderate homocysteinemia > 30-100 Therapy necessary!
Severe homocysteinemia > 100 Therapy necessary!

Notice:

  • Women have low regular homocysteine concentrations than men.
  • With age, homocysteine levels increase, in men already from the age of 45, in women after menopause (= last menstrual period in a woman’s life, without removal of the uterus).
  • Hyperhomocysteinemia is common in chronic renal failure (kidney weakness). Causes are lack of excretion of homocysteine, the catabolic state and latent vitamin deficiency.

For details on therapy, see below Hyperhomcysteinemia/Further therapy. Further notes

  • Homocysteinemia is an independent risk factor for vascular disease (vascular disease), especially myocardial infarction (heart attack) and apoplexy (stroke), but also for peripheral arterial occlusive disease (PAVD).
  • According to a consensus paper written by experts, it is possible to prevent about 25 percent of cardiovascular events – myocardial infarction (heart attack) or apoplexy (stroke) – by lowering homocysteine levels.
  • If the homocysteine level increases by only 0.5 µmol/l, the risk of myocardial infarction increases by 2.5 times and the risk of apoplexy (stroke) and arterial occlusive disease increases even 5 times.
  • New research also indicates that homocysteinemia is an independent risk factor for vascular (vessel-related) dementia as well as Alzheimer’s disease.

Further diagnostics

  • If it is an acquired homocysteinemia, an additional determination of vitamins can be made:
    • Vitamin B6 (pyridoxine)
    • Vitamin B12 (cobalamin)
    • Folic acid