Homocysteine auto-oxidizes and reacts with reactive oxygen intermediates, damaging endothelial cells and increasing the risk of thrombus formation. Ectopia lentis
Homocystinuria is the second most common cause of heritable ectopia lentis. Homocystinuria is an autosomal recessive metabolic disorder most often caused by a near absence of cystathionine b-synthetase. It is associated with intellectual disability, osteoporosis, chest deformities, and increased risk of thrombotic episodes. Lens dislocation occurs in 90% of patients, and is thought to be due to decreased zonular integrity due to the enzymatic defect. Lens dislocation in homocystinuria is usually bilateral and in 60% of cases occurs in the inferior or nasal direction. Causes
Vitamin deficiency
Deficiencies of vitamins B6, B9 and B12 can lead to high homocysteine levels. Vitamin B12 acts as a cofactor for the enzyme methionine synthase (which forms part of the S-adenosylmethionine (SAM) 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). Alcohol
Chronic consumption of alcohol may also result in increased plasma levels of homocysteine. Tobacco
Smokeless tobacco is implicated as risk factor for hyperhomocysteinemia. Smoking also causes hyperhomocysteinemia

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. About 50% of homocysteine is converted back to methionine by remethylation via the methionine synthase major pathway.
When combined with medicine to reduce blood pressure (antihypertensive drugs), it is not clear if treatments that lower homocysteine can help prevent a stroke in some people. 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. See also
Homocystinuria
Kilmer S. McCully

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