Cerebrospinal fluid methylmalonic acid levels in normal subjects and patients with cobalamin deficiency

We measured methylmalonic acid, which accumulates in the blood and tissues of patients with cobalamin deficiency, in the CSF of 65 patients using capillary-gas chromatography and mass spectrometry. In 58 control patients, methylmalonic acid concentrations were always higher in CSF than in serum (mean CSF: serum ratio, 2.65; range, 1.17 to 7.78). In contrast, in six patients with elevated serum methylmalonic acid levels due to renal failure, CSF concentrations were normal in five and the CSF: serum ratio was less than one in four. In three patients with neuropsychiatric syndromes due to cobalamin deficiency and one patient with a normal serum cobalamin level who was an abuser of nitrous oxide, CSF concentrations were markedly increased (mean level, 600 times that of controls), out of proportion to those in the serum (mean CSF: serum ratio, 8.38; range, 3.5 to 13.5). The potential usefulness of CSF metabolite levels in the diagnosis of cobalamin deficiency is undetermined.