Abnormal Propionic-Methylmalonic-Succinic Acid Metabolism in Vitamin B12 Deficiency and Its Possible Relationship to the Neurologic Syndrome of Pernicious Anemia

Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry.

“…A correlation between Cbl levels and levels of urinary methylmalonic acid was observed previously in some studies (3, 5) but not in others (1,8,9). The failure to find correlations between serum methylmalonic acid levels and any of the hematologic parameters, except for a weak inverse correlation with platelet count, is in agreement with studies employing levels of urinary methylmalonic acid (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

“…Previous workers, studying small numbers of patients with neurologic abnormalities, have found no correlation with urine levels of methylmalonic acid (3,4,8,9) or have suggested a possible relationship (2,(10)(11)(12). The positive correlation between serum methylmalonic acid levels and the presence of neurologic abnormalities in our large series of patients is of interest, since the biochemical mechanisms responsible for the neurologic abnormalities in Cbl deficiency are still unknown.…”

“…Previous investigators have shown that most patients with cobalamin (Cbl, vitamin B12)' deficiency have elevated levels of methylmalonic acid in their urine (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The origin of the methylmalonic acid has recently been elucidated (13) and is illustrated in Fig.…”

“…More rarely, diagnostic problems can also develop in patients with hematologic abnormalities, since serum Cbl levels may be normal in Cbl-deficient patients who have elevated levels ofCblbinding proteins (24). Additional diagnostic tests like urinary methylmalonic acid (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and the deoxyuridine suppression test (25,26) have not been widely used and, thus, a definite need exists for additional tests that could be used to evaluate patients for Cbl deficiency and to evaluate the sensitivity and specificity of the serum Cbl assay.…”

Myelin

“…A clinical study showed that a patient with pernicious anemia showing neurological abnormalities excreted more methylmalonic acid than did patients with only hematological abnormalities. Furthermore, 14C from propionate injected into this patient was detected in a nerve by autoradiography, after subsequent biopsy, whereas injected isotope from propionate did not accumulate in the nerve from a patient without neurological symptoms (Vivaqua et al, 1966). In addition, suralnerve biopsies from pernicious anemia patients incorporated 14C-Iabeled propionate, in vitra, into abnormal (branched-chain and odd-numbered) fatty acids (Frenkel, 1971).…”