The Excretion of Methylmalonic Acid and Succinic Acid in Vitamin B12 and Folate Deficiency

The excretion of methylmalonic acid (MMA) and of succinic acid was measured in 18 control subjects and in 58 patients with vitamin B₁₂ and/or folate deficiency. The 18 control subjects excreted from 0.0 to 3·5 mg. MMA in 24 hours. MMA excretion was raised in 27 of 41 patients (Group I) with conditions associated primarily with B₁₂ deficiency. These 27 patients included 15 patients with Addisonian pernicious anaemia, two patients following total gastrectomy, two patients with anatomical lesions of the small intestine and eight patients following partial gastrectomy, whereas MMA excretion was normal in four patients with atrophic gastritis and in a further 10 patients following partial gastrectomy. In Group I, MMA excretion was raised in all but one of the patients with serum B₁₂ levels less than 100 pg./ml. due to uncomplicated B₁₂ deficiency, but was invariably normal in patients with borderline serum B₁₂ levels (from 100 to 160 pg./ml.). In the patients with serum B₁₂ levels less than 100 pg./ml., with associated iron and/or folate deficiency, the excretion of MMA tended to be lower than in patients with uncomplicated B₁₂ deficiency, and was often normal. MMA excretion was slightly raised in one of 17 patients with megaloblastic anaemia, primarily due to folate deficiency (Group II), although six of them had serum B₁₂ levels less than 100 pg./ml. The patient with a raised MMA excretion needed B₁₂ therapy for a full haematological remission. The 18 control subjects excreted from 2.0 to 12.5 mg. succinic acid in 24 hours. Succinic acid excretion was subnormal in nine and raised in five patients in Group I. These 14 patients all had serum B₁₂ levels less than 100 pg./ml. None of the Group II patients excreted subnormal amounts of succinic acid but three, including two patients with serum B₁₂ levels less than 100 pg./ml., excreted raised amounts of succinic acid.