[P-methylmalonate and P-homocysteine: metabolic markers of vitamin deficiencies. Background, validity and applications].

The clinical value of measuring concentrations of methylmalonate and total homocysteine in plasma as an aid in the diagnosis of cobalamin, folate and pyridoxine deficiencies has recently aroused interest. This review describes factors which affect the validity and interpretation of plasma (p-) methylmalonate and p-homocysteine. P-methylmalonate is not affected by preanalytical variables, there are no age- or sex-related differences and the intra-individual variation is negligible. The only important limitation to the specificity of an increased p-methylmalonate for cobalamin deficiency appears to be secondary accumulation due to impaired renal function. However, an elevated p-methylmalonate, which normalizes following cobalamin injections proves cobalamin deficiency, irrespective of renal function. P-homocysteine is affected by several preanalytical factors, so the utmost care is required in blood collection. Furthermore, p-homocysteine is dependent on age and sex. An elevated p-homocysteine is a less specific parameter for cobalamin deficiency, for which reason measurement in patients with suspected cobalamin deficiency is indicated only if p-methylmalonate is normal. Homocysteine is also increased in folate and pyridoxine deficiencies. Recently, moderate hyperhomocysteinaemia has become an established independent and significant risk factor for premature atherosclerotic cardiovascular diseases, suggesting a large future demand for p-homocysteine determinations.