http://www2.kemc.co.uk/clients/msrc04/d ... isease.pdf
Plasma homocysteine has repeatedly been identified as a strong independent risk factor for cardiovascular disease, as well as several other disorders...
Krumdieck and Prince (34), for example, have called attention to the close parallels between the hallmark manifestations of homocystinuria (with serum homocysteine concentrations typically >100 µm/L), ie, occlusive vascular disease, osteoporosis, mental deterioration, and
ectopia lentis, and the counterpart manifestations of “normal” aging (with serum homocysteine concentrations between 10 and 100 µm/L), ie, occlusive vascular disease, osteoporosis, dementia, and
presbyopia.
http://nopr.niscair.res.in/handle/123456789/3401
Biochemistry of homocysteine in health and diseases
The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In
normal circumstances, it is
converted to cysteine and partly remethylated to methionine with the help of
vit B12 and folate. However, when normal metabolism is disturbed, due to
deficiency of cystathionine-b-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A
decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only),
ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms.
[hmmm...] Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins, (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.
if a patient happens to be Type 1 - interesting, interesting...:
http://atvb.ahajournals.org/cgi/content ... 21/12/2080
Vascular Outcome in Patients With Homocystinuria due to Cystathionine ß-Synthase Deficiency Treated Chronically
An inborn error of metabolism, homocystinuria due to cystathionine ß-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess the effectiveness of long-term homocysteine-lowering treatment in reducing vascular risk in 158 patients. Vascular outcomes were analyzed and effectiveness of treatment in reducing vascular risk was evaluated by comparison of actual to predicted number of vascular events, with the use of historical controls from a landmark study of 629 untreated patients with cystathionine ß-synthase deficiency. The 158 patients had a mean (range) age of 29.4 (4.5 to 70) years; 57 (36%) were more than 30 years old, and 10 (6%) were older than 50 years. There were 2822 patient-years of treatment, with an average of 17.9 years per patient. Plasma homocysteine levels were markedly reduced from pretreatment levels but usually remained moderately elevated. There were 17 vascular events in 12 patients at a mean (range) age of 42.5 (18 to 67) years: pulmonary embolism (n=3), myocardial infarction (n=2), deep venous thrombosis (n=5), cerebrovascular accident (n=3), transient ischemic attack (n=1), sagittal sinus thrombosis (n=1), and abdominal aortic aneurysm (n=2). Without treatment, 112 vascular events would have been expected, for a relative risk of 0.09 (95% CI 0.036 to 0.228; P<0.0001). Treatment regimens designed to lower plasma homocysteine significantly reduce cardiovascular risk in cystathionine ß-synthase deficiency despite imperfect biochemical control. These findings may be relevant to the significance of mild hyperhomocysteinemia that is commonly found in patients with vascular disease...
There is now evidence that early treatment delays or prevents ectopia lentis.
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