Recommended approaches for the laboratory measurement of homocysteine in the diagnosis and monitoring of patients with hyperhomocysteinaemia

Several recent studies have indicated that an increased concentration of pl asma homocysteine is an independent risk factor for the premature developme nt of vascular disease. These important findings emphasize the need for car eful selection of an appropriate analytical approach to diagnose and treat individuals who may be at risk. We compared the results obtained from the m easurement of plasma total homocysteine (free + protein-bound fractions) by high-performance liquid chromatography (HPLC) with the measurement of plas ma free homocystine (free fraction) by conventional ion-exchange chromatogr aphy in 10 patients with inherited defects of homocysteine metabolism and 1 3 obligate heterozygote individuals. This study can be used to formulate re commendations on the appropriate use of these assays in different clinical circumstances. Our results show that the concentration of total plasma homo cysteine must exceed 60 mu mol/L before plasma free homocystine becomes det ectable by conventional ion-exchange chromatography. Similarly, assessment of the urinary excretion of homocysteine in these patients indicates that i t may not become consistently detectable by conventional ion-exchange chrom atography or HPLC until plasma total homocysteine exceeds 150 mu mol/L. On this basis, while most patients with classical homocystinuria would be d etected by analysis of plasma using conventional ion-exchange chromatograph y or by measurement of of the urinary homocysteine excretion, occasional pa tients would be missed. When monitoring patients receiving treatment for cl assical homocystinuria, in whom metabolic control is good, and when investi gating individuals with a suspected inherited defect of cobalamin or folate metabolism, a method which measures plasma total homocysteine should be us ed. The identification of moderate hyperhomocysteinaemia of undefined cause investigated in relation to a history of early vacsular disease can only b e identified by this approach.