ICD-9-CM 270.4 eMedicine neuro/578 | DiseasesDB 29853 | |
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Hyperhomocysteinemia or hyperhomocysteinaemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 µmol/L.
Contents
- Signs and symptoms
- Cardiovascular risks
- Neuropsychiatric illness
- Bone health
- Causes
- Genetic
- Diagnosis
- Treatment
- References
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.
Hyperhomocysteinemia is typically managed with vitamin B6, vitamin B9 and vitamin B12 supplementation. Supplements of these vitamins; however, do not change 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 and 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 and Alzheimer's 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. Homocysteine auto-oxidizes and reacts with reactive oxygen intermediates, damaging endothelial cells and increasing the risk of thrombus formation.
Causes
Deficiencies of vitamins B6, B9, and B12 can lead to high homocysteine levels. Vitamin B12, or cobalamin, acts as a cofactor for the enzyme methionine synthase (which forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle). Vitamin B12 deficiency prevents the 5-methyltetrahydrofolate (5-MTHF) form of folate from being converted into THF due to the "methyl trap". This disrupts the folate pathway and leads to an increase in homocysteine which damages cells (for example, damage to endothelial cells can result in increased risk of thrombosis).
Chronic consumption of alcohol may also result in increased plasma levels of homocysteine.
Genetic
Homocysteine is a non-protein amino acid, synthesized from methionine and either recycled back into methionine or converted into cysteine with the aid of the B-group vitamins.
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 world's population.Elevations of homocysteine can also occur in the rare hereditary disease homocystinuria.
Diagnosis
Blood sampling
Treatment
Vitamins B6, B9, or B12 supplements, while they lower homocysteine level do not change the risk of heart disease, stroke, or death. This also applies to people with kidney disease on dialysis.
Hypotheses have been offered to address the failure of homocysteine-lowering therapies to reduce cardiovascular events. When folic acid is given as a supplement, it may increase the build-up of arterial plaque. A second hypothesis involves the methylation of genes in vascular cells by folic acid and vitamin B12, which may also accelerate plaque growth. Finally, altered methylation may catalyse l-arginine to asymmetric dimethylarginine, which is known to increase the risk of vascular disease.