This requires active folate and vitamin B12, in order to donate a methyl group. Active folate is known as 5-methyltetrahydrofolate (5-MTHF). Another pathway for the conversion of homocysteine back to methionine also exists, involving methylation with trimethylglycine (also called betaine or abbreviated to TMG) as a methyl donor. The remaining homocysteine is transsulfurated to cysteine, with vitamin B6 as the co-factor.Genetic defects in 5-MTHF reductase can consequently lead to hyperhomocysteinemia. The most common polymorphisms are known as MTHFR C677T and MTR A2756G. These polymorphisms occur in about 10% of the worlds population. Elevations of homocysteine can also occur in the rare hereditary disease homocystinuria. Diagnosis
A blood test can be performed to quantify total homocysteine concentration in the plasma, of which approximately 80% is generally protein-bound. Classification of hyperhomocysteinemia is defined with respect to serum concentration as follows:
Moderate: 15–30 nmol/mL (or μmol/L)
Intermediate: 30–100 nmol/mL
Severe: > 100 nmol/mLIf total homocysteine concentration is not found to be elevated, but clinical suspicion is still high, an oral methionine loading challenge several hours prior to quantification of homocysteine concentration may be used to increased sensitivity for marginal abnormalities of homocysteine metabolism.Fasting for 10 hours is sometimes recommended prior to measurement of homocysteine levels, but this may not be necessary for diagnostic yield. Treatment
Vitamins B6, B9, or B12 supplements (alone or combined), while they lower homocysteine level, do not change the risk of heart disease or prevent death in people who have heart disease when compared to standard care or to an inactive supplement in a clinical trial.
Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 μmol/L.As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of
vitamin B6, folic acid (vitamin B9), and vitamin B12 can lead to high homocysteine levels. Other possible causes of hyperhomocysteinemia include genetics, excessive methionine intake, and other diseases. Hyperhomocysteinemia is typically managed with vitamin B6, vitamin B9 and vitamin B12 supplementation. Hyperhomocysteinemia is a risk factor for cardiovascular disease; however, supplements of these vitamins may not improve cardiovascular disease outcomes. Signs and symptoms
Elevated levels of homocysteine have been associated with a number of disease states. Cardiovascular risks
Elevated homocysteine is a known risk factor for cardiovascular disease as well as thrombosis. It has also been shown to be associated with microalbuminuria which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Homocysteine degrades and inhibits the formation of the three main structural components of arteries: collagen, elastin and proteoglycans. In proteins, homocysteine permanently degrades cysteine disulfide bridges and lysine amino acid residues, affecting structure and function. Neuropsychiatric illness
Evidence exists linking elevated homocysteine levels with vascular dementia and Alzheimers disease. There is also evidence that elevated homocysteine levels and low levels of vitamin B6 and B12 are risk factors for mild cognitive impairment and dementia. Oxidative stress induced by homocysteine may also play a role in schizophrenia. Bone health
Elevated levels of homocysteine have also been linked to increased fractures in elderly persons.