Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition

Abstract

Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders afffecting homocysteine (Hcy) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcy. A nutritional approach to HHcy management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate that are crucial for Hcy conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcy remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcy metabolism. For individuals with HHcy, maintaining a plasma Hcy concentration below 50 μmol/L consistently is vital to lowering the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing the specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.

Keywords: Marfanoid habitus; betaine; ectopia lentis; homocysteine; homocystinuria; hyperhomocysteinemia; inborn metabolic diseases; remethylation; thrombotic events; transsulfuration.

Figure 1

Homocysteine (Hcy) metabolism. Hcy is remethylated into methionine (Met) by methionine synthase (MS) in the presence of vitamin B12 and folates; transsulfuration by cystathionine-β-synthase (CβS), whose cofactor is vitamin B6, allows Hcy to be transformed into cysteine (Cy) and then into sulfate. MTHF-R: methylenetetrahydrofolate reductase.

Figure 2

Categories of hyperhomocysteinemia (mild, moderate, and severe), based on plasma homocysteine levels [17].

Figure 3

Diagnostic algorithm for hyperhomocysteinemias [17,67] for a cutoff of 30 μmol/L. Cbl: cobalamin; MMA: methylmalonic aciduria; CBS: cystathionine β-synthase deficiency; MTHF-R: methylenetetrahydrofolate reductase.