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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]
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]
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.
Treatment may include dietary changes and folic acid supplements. [1] Dietary changes including eating foods high in folate such as, fruits and green leafy vegetables can help. [1] Prevention is recommended for pregnant women or those who are planning a pregnancy. [1] Folate deficiency is very rare in countries with folic acid fortification ...
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.
Elevated MMA levels may also be due to the rare metabolic disorder combined malonic and methylmalonic aciduria (CMAMMA). [117] [118] Folate deficiency is treated with supplemental oral folic acid of 400 to 1000 μg per day. This treatment is very successful in replenishing tissues, even if deficiency was caused by malabsorption.
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The US Food and Drug Administration (FDA) approved betaine trimethylglycine (also known by the brand name Cystadane) for the treatment of homocystinuria, a disease caused by abnormally high homocysteine levels at birth. [22] Trimethylglycine is also used as the hydrochloride salt (marketed as betaine hydrochloride or betaine HCl).
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