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As an aid for screening patients suspected of having an inherited disorder of methionine metabolism including:
-Cystathionine beta-synthase deficiency (Homocystinuria)
-Methylenetetrahydrofolate reductase deficiency (MTHFR) and its thermolabile variants:
- Methionine synthase deficiency
-Cobalamin (Cbl) Metabolism:
- Combined Methyl-Cbl and Adenosyl-Cbl deficiencies: Cbl C2, Cbl D2 and Cbl F3 deficiencies
- Methyl-Cbl specific deficiencies: Cbl D-Var1, Cbl E and Cbl G deficiencies
-Transcobalamin II deficiency:
- Adenosylhomocysteinase: AHCY deficiency
- Glycine N-methyltransferase: GNMT deficiency
- Methionine Adenosyltransferase I/III Deficiency: MAT I/III deficiency
As a (weak) indicator of cardiovascular risk
To be used in conjunction with plasma amino acids and urine organic acids to aid in the biochemical screening for primary and secondary disorders of methionine metabolism.
Homocysteine is an intermediary in the sulfur-amino acid metabolism pathways, linking the methionine cycle to the folate cycle. Inborn errors of metabolism that lead to homocysteinemia/-uria include cystathionine beta-synthase deficiency (homocystinuria) and various defects of methionine re-methylation.
Homocysteine also was thought to be an independent predictor of cardiovascular disease (atherosclerosis, heart disease, thromboembolism), as early observational studies prior to 2000 linked homocysteine to cardiovascular risk and morbidity and mortality. However, following FDA-mandated folic acid supplementation in 1998, homocysteine concentrations decreased by approximately 10% without a similar change in cardiovascular or ischemic events. Currently, the use of homocysteine for assessment of cardiovascular risk is uncertain and controversial. Based on several meta-analyses, at present, homocysteine may be regarded as a weak risk factor for coronary heart disease, and there is a lack of direct causal relationship between hyperhomocysteinemia and cardiovascular disease. It is most likely an indicator of poor lifestyle and diet.
Adults: 0-9 mcmol/g creatinine
Hyperhomocysteinuria could be caused by either genetic or nutritional factors. While the highest levels are characteristic of classic homocystinuria, there are no reliable cut-offs to differentiate between genetic or dietary causes of elevated homocysteine (HCY) levels. In our experience, very high HCY levels have been seen in some patients with cystathione beta-synthase deficiency.
HCY levels >9 mcmol/g creatinine are considered abnormal in patients under evaluation for cardiovascular or neurovascular disease.
Response to dietary treatment can be better evaluated by monitoring plasma homocysteine (HCYSP / Homocysteine, Total, Plasma) levels over time.
1. Mudd SH, Levy HL, Kraus JP: Disorders of transsulfuration. In The Metabolic and Molecular Basis of Inherited Disease. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw Hill Book Company, 2001, pp 2007-2056
2. Klee GG: Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem 2000;46(B):1277-1283