Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence

The concentration of total homocysteine (tHcy) in serum and plasma is elevated in both folate and cobalamin deficiencies, whereas methylmalonic acid (MMA) in serum, plasma, or urine is a specific marker of cobalamin function. The combined measurement of both metabolites is useful for the diagnosis and follow-up of these deficiency states. In addition, tHcy is elevated under various pathologic states (eg, renal failure), and hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, cognitive dysfunction, and adverse pregnancy outcomes. The diagnostic utility of tHcy and MMA concentrations as markers of folate and cobalamin deficiencies in healthy and diseased children has been documented. This article briefly summarizes the biochemical background of tHcy and MMA and the associations of tHcy and MMA with various disease states and focuses on novel data obtained in infants, children, and adolescents, with emphasis on cobalamin status in infants. The utility of tHcy and MMA as indicators of cobalamin and folate deficiencies in adults can be extended to infants and older children. Furthermore, as in adults, tHcy is related to unhealthy lifestyle factors and is a risk factor for vascular disease. High MMA concentrations in newborns, occasionally denoted as benign methylmalonic aciduria, may reflect impaired cobalamin function.