Table 1

Differential diagnosis of a high plasma homocysteine

Causes of an elevated plasma homocysteine concentration
tHCy 15–40 μmol/LtHCy 40–100 μmol/LtHCy >100 μmol/L

  • Nutritional vitamin B12 or folate deficiency

  • Mild chronic kidney disease (other than that associated with cobalamin disorders)

  • Drugs affecting HCy, folate or cobalamin metabolism (nitrous oxide, folate antagonist medication)

  • Suboptimal sample handling

  • MTHFR polymorphisms (including c.677 C>T variant)

  • MTHFR

  • MTHFR polymorphisms combined with nutritional folate deficiency

  • Genetic disorders of cobalamin absorption or transport

  • Moderate/severe nutritional B12 or folate deficiency (including malabsorption syndromes and pernicious anaemia)

  • Moderate/severe chronic kidney disease

  • Classical homocystinuria

  • Cobalamin disorders

  • MTHFR

  • MTHFR, methyltetrahydrofolate reductase; tHCy, total homocysteine.