[Measurement of methylmalonic acid, homocysteine and methionine in cobalamin and folate deficiencies and homocysteinuria]

• BACKGROUND: Deficiencies of cobalamin (vitamin B12) or folate are common conditions that predispose for anemia and chronic diseases. An elevated concentration of methylmalonic acid in plasma/serum is an indicator of cobalamin deficiency, whereas an increased concentration of total homocysteine in plasma occurs with deficiency of both cobalamin and folate. The biomarkers methylmalonic acid and homocysteine are therefore complementary, and the combination is often requested when conventional tests fail to provide an unambiguous diagnosis. MATERIAL AND METHODS: This article summarizes publications, retrieved through Medline, describing novel strategies for laboratory diagnostics of cobalamin and folate deficiencies. RESULTS AND INTERPRETATION: Adverse health effects of food fortification and uncritical supplementation with folic acid are explanations for a renewed interest in individual diagnosis of B-vitamin deficiency. Interpretation of methylmalonic acid and homocysteine test results requires knowledge of kidney function, as renal failure causes an increase in the concentrations of both metabolites. Homocystinuria is a condition that also causes increased levels of plasma homocysteine. This condition is an inborn error with a higher prevalence (1 : 6400) than previously recognized; which usually responds favourably to homocysteine-lowering therapy. Patients with homocysteinuria have high levels of methionine in plasma and knowledge of plasma methionine concentration may therefore distinguish these patients from those with conditions like B-vitamin deficiencies or renal failure, which are accompanied by normal or low to normal methionine concentrations. Complementarity, logistics, small sample volumes and costs therefore favour a combined analysis of methylmalonic acid, homocysteine and methionine in a single sample. Such an approach also allows assessment of cobalamin status in small volume capillary blood samples drawn from newborns and infants.

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