Summary: Organic acids in plasma and urine of a patient with isovaleric acidemia were measured serially during a severe ketoacidotic attack. Urinary ketone bodies, lactic acid and 2-hydroxy-n-butyric acid changed in parallel with the plasma isovaleric acid concentration, which was correlated closely with the severity of the clinical symptoms. A 2-day lag was observed between the time of the peak plasma isovaleric acid level and that of the highest urinary excretion of 3-hydroxyisovaleric acid, methylsuccinic acid, mesaconic acid and 2-hydroxyisobutyric acid, the total quantity of which amounted to one-third of that of isovalerylglycine on the 4th day of the attack. Urinary isovalerylglycine excretion remained at a plateau for 4 days after the highest level of plasma isovaleric acid was observed. The decrease of urinary hippuric acid excretion during the attack continued until the patient had recovered enough to be able to eat. Benzoic acid administration concomitant with leucine and glycine canceled the effect of glycine in lessening the rise of plasma isovaleric acid concentration after a leucine load.
Speculation: Whereas the glycine-conjugating pathway plays a major role in clearing accumulated isovaleryl-CoA and isovaleric acid in isovaleric acidemia, μ- and (μ-l)-oxidation systems may also make a considerable contribution to detoxifying isovaleric acid, because their metabolites are excreted in large quantities in the urine. The present study shows, however, that these oxidaton systems cannot function effectively in the early stage of a severe attack and that the capacity of the glycine-conjugating pathway is not sufficient, so other methods of removing accumulated isovaleric acid in body fluids, such as blood exchange transfusion, may be needed.
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Shigematsu, Y., Sudo, M., Momoi, T. et al. Changing Plasma and Urinary Organic Acid Levels in a Patient with Isovaleric Acidemia during an Attack. Pediatr Res 16, 771–775 (1982) doi:10.1203/00006450-198209000-00013
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