Hyperhomocysteinemia: Clinical Insights

Homocysteine (Hcy) is a sulfhydryl-containing amino acid, and intermediate metabolite formed in metabolising methionine (Met) to cysteine (Cys); defective Met metabolism can increase Hcy. The effect of hyperhomocysteinemia (HHcy) on human health, is well described and associated with multiple clinical conditions. HHcy is considered to be an independent risk factor for common cardiovascular and central nervous disorders, where its role in folate metabolism and choline catabolism is fundamental in many metabolic pathways. HHcy induces inflammatory responses via increasing the pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines which lead to Hcy-induced cell apoptosis. Conflicting evidence indicates that the development of the homocysteine-associated cerebrovascular disease may be prevented by the maintenance of normal Hcy levels. In this review, we discuss common conditions associated with HHcy and biochemical diagnostic workup that may help in reaching diagnosis at early stages. Furthermore, future systematic studies need to prove the exact pathophysiological mechanism of HHcy at the cellular level and the effect of Hcy lowering agents on disease courses.