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Methylmalonic Acid Excretion in Vitamin B 12 Deficiency
Author(s) -
Bashir Helen V.,
Hinterberger H.,
Jones B. P.
Publication year - 1966
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1966.tb00156.x
Subject(s) - methylmalonic acid , excretion , urine , medicine , hydroxocobalamin , cyanocobalamin , vitamin b12 , cobalamin , vitamin , endocrinology , methylmalonic aciduria , urinary system , chemistry , gastroenterology
methylmalonic acid was first isolated from pooled human urine in 1957 by Thomas and Stalder and convincing evidence has since been obtained to show that in man the isomerization of l‐methylmalonyl‐Co A to succinyl‐Co A is dependent on the B 12 coenzyme dimethylbenzimidazolyl cobamide (White, 1962). Indeed, Cannata, Focesi, Mazumder, Warner and Ochoa (1965) showed recently that l‐methylmalonyl‐Co A mutase bears two molecules of cobamide coenzyme firmly attached to its molecule. In a series of 30 patients Cox and White (1962) detected excessive methylmalonic acid in the urine of all patients with serum vitamin B 12 levels below 140 pg./ml., their lower limit of normal. Patients with normal serum B 12 levels excreted up to 4 mg. of methylmalonic acid in 24 hours. Their series included six patients who were treated with intramuscular hydroxocobalamin (1000 μg.). In five of these, excretion fell to normal within 3 days, and on the fifth day after injection in the sixth patient. Barness, Young, Mellman, Khan and Williams (1963) reported one vitamin B 12 deficient patient in whom the urinary excretion of methylmalonic acid reached 500 mg. in 24 hours. Recently Khan, Williams, Barness, Young, Shafer, Vivacqua and Beaupre (1965) have described seven out of nine patients with pernicious anaemia in whom methylmalonic acid excretion persisted for some months after the institution of B 12 therapy. This occurred despite full clinical and haematological remissions and in four patients, normal serum vitamin B 12 levels. The present study was undertaken to determine the value of urinary methylmalonic acid excretion as a screening test for vitamin B 12 deficiency. The estimation of methylmalonic acid was carried out by a rapid thin layer chromatographic technique, suitable for routine laboratory use. Normal controls and patients suffering from general haematological and medical disorders were screened as well as patients suffering from megaloblastic anaemia. In several patients the excretion of methylmalonic acid was followed for a short period after B 12 therapy.