Indications

Deficiencies in Vitamin B12 and/or folate can lead to elevated homocysteine levels. Genetic defects can also cause moderately to significantly elevated homocysteine levels. Additionally, a deficiency in Vitamin B6 can result in increased homocysteine concentrations. Elevated homocysteine is a biochemical marker associated with cardiovascular disease. For a more comprehensive evaluation, complementary tests such as serum methylmalonate (S-MMA) may be recommended.

Additional Information

Homocysteine is an intermediate in the metabolism of methionine. The remethylation of homocysteine to methionine requires cobalamin (Vitamin B12) and methyltetrahydrofolate. Homocysteine is also metabolized by condensing with serine to form cystathionine, a process that requires pyridoxal phosphate (Vitamin B6). Deficiencies in Vitamin B12, Vitamin B6, or folic acid can result in elevated homocysteine levels in the blood. Additionally, mutations in genes related to cystathionine beta-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), or enzymes involved in cobalamin synthesis can also lead to increased homocysteine concentrations.

Homocystinuria

Homocystinuria is an autosomal recessive disorder caused by a defective cystathionine beta-synthase enzyme (CBS), leading to the accumulation of homocysteine and methionine within cells. A complete enzyme deficiency results in symptoms such as lens dislocation, skeletal deformities, intellectual disability, and thromboembolic complications, whereas partial deficiencies mainly result in thromboembolic issues.

Homocysteine has a strong tendency to bind with other sulfur-containing compounds, including other homocysteine molecules, forming homocysteine. Elevated levels of homocystine can be detected in urine, but diagnosis is primarily confirmed through plasma analysis of homocysteine and methionine. This specialized analysis is performed by the Center for Inherited Metabolic Diseases at Karolinska University Laboratory.

Treatment

Vitamin B6 is a necessary cofactor for CBS, and some patients with partial enzyme deficiency may benefit from Vitamin B6 supplementation to enhance residual enzyme activity. For unexpectedly high plasma homocysteine levels, consultation with the Center for Inherited Metabolic Diseases at Karolinska University Laboratory (Huddinge) is recommended for further evaluation.

Source

Karolinska University Laboratory - Homocysteine Testing