Table 1 Causes of Hyperhomocysteinemia
From: Impaired Homocysteine Metabolism and Atherothrombotic Disease
Genetic factors | Relationship |
|---|---|
MTHFR defect (activity < 20%) | Homozygous thermostable mutations (rare), severe basal hyperhomocysteinemia under fasting conditions |
MTHFR deficiency (activity < 50%) | Homozygous thermolabile C677T mutation (10%), moderate basal hyperhomocysteinemia |
CBS defect (activity < 2%) | Homozygotes (rare), severe basal hyperhomocysteinemia |
CBS deficiency | Heterozygotes (0.5–1.5%), abnormal postmethionine-load increase of homocysteine above fasting values |
Functional methionine synthase deficiency | Altered cobalamin metabolism (rare mutations), intermediate to severe basal hyperhomocysteinemia |
Nutritional factors | Relationship |
Vitamin B6 deficiency | Abnormal postmethionine-load increment of homocysteinemia |
Vitamin B12 deficiency | Moderate to intermediate basal hyperhomocysteinemia |
Folate deficiency | Moderate to intermediate basal hyperhomocysteinemia |
Excess of methionine-rich animal proteins | Moderate to intermediate basal hyperhomocysteinemia and postmethionine-load hyperhomocysteinemia? |
Physiologic factors | Relationship |
Aging | Plasma homocysteine levels increase with age |
Male sex | Men have higher basal homocysteinemia than women |
Menopause | Increased homocysteine levels in postmenopausal women that could be reduced by hormone replacement therapy |
Race | Black South-Africans have lower homocysteine levels than the White population |
Pathologic factors | Relationship |
Tobacco smoking | Altered folate metabolism and vitamin B6 deficiency? |
Alcoholism | Altered folate metabolism? |
Decreased renal function | Reduced renal clearance of homocysteine |
Psoriasis | Defect of intracellular homocysteine use? |
Cancer | Defect of intracellular homocysteine use? |
Cardiac or renal transplantations | Folate and vitamin B6 deficiency and reduced renal clearance of homocysteine |
Iatrogenic factors | Relationship |
Oral contraceptives | Altered folate metabolism and vitamin B6 deficiency? |
Methotrexate | Dihydrofolate reductase inhibition |
Nitrous oxide (N2O) | Methionine synthase inhibition |
Anticonvulsants | Altered folate metabolism |
Sulfasalazine | Inhibition of folate absorption |
