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Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of total homocysteine (that is, including homocystine and homocysteine-cysteine disulfide) in the blood, conventionally described as above 15 μmol/L. [1]
In the body, homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin B 6, B 9, and B 12. [3] High levels of homocysteine in the blood (hyperhomocysteinemia) is regarded as a marker of cardiovascular disease, likely working through atherogenesis, which can result in ischemic injury.
Methylenetetrahydrofolate reductase deficiency is the most common genetic cause of elevated serum levels of homocysteine (hyperhomocysteinemia). It is caused by genetic defects in MTHFR, which is an important enzyme in the methyl cycle. [1] Common variants of MTHFR deficiency are asymptomatic and have only minor effects on disease risk. [2]
For most substances presented, the optimal levels are the ones normally found in the population as well. More specifically, optimal levels are generally close to a central tendency of the values found in the population. However, usual and optimal levels may differ substantially, most notably among vitamins and blood lipids, so these tables give ...
A serum folate level of less than 7 nmol/L (3 μg/L) is indicative of folate deficiency; Red blood cell folate testing is not routinely performed, since serum folate is sufficient in most cases, however, if there is a strong suspicion of folate deficiency despite a normal serum folate level, a red cell folate test may be performed.
Deficiency can develop without anemia or within normal vitamin B 12 levels, leading to a methylmalonic acid or homocysteine assay. [ 2 ] [ 4 ] [ 143 ] [ 144 ] In some cases, a peripheral blood smear may be used; which may allow to show macrocytes and hypersegmented polymorphonuclear leukocytes . [ 141 ]
Patients exhibit developmental delay, motor and gait dysfunction, seizures, and neurological impairment and have extremely high levels of homocysteine in their plasma and urine as well as low to normal plasma methionine levels. This deficiency and mutations in MTHFR have also been linked to recessive spastic paraparesis with complex I deficiency.
Elevated homocysteine is an independent risk factor for cardiovascular disease and inversely correlated to consumed vitamin B12/B6 and folate levels. [37] Homocysteine methylation to methionine is catalyzed by MTR, resulting in appropriate intracellular levels of methionine and tetrahydrofolate, alongside non-toxic homocysteine levels.
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