Organic acids and branched-chain amino acids in body fluids before and after multiple exchange transfusions in maple syrup urine disease

Abstract

We successfully treated a critically ill infant with the classical type of maple syrup urine disease by multiple exchange tranfusions via a peripheral artery and vein and with positive supplementation in the early stage of therapy. Clinical improvement was definite after the plasma leucine level fell below 1 mmol/l. There was a close linear correlation between plasma concentrations of branched-chain amino acids and their corresponding branched-chain α-keto acids and branched-chain α-hydroxy acids. α-Hydroxy acids were more easily excreted in the urine than α-keto acids and amino acids. Our studies on urinary organic acids supported the existence of minor metabolic pathways of branched-chain α-keto acids, although they were not though to be important in eliminating accumulated α-keto acids. Urinary excretion of succinic acid and α-ketoglutaric acid, which are components of the citric acid cycle, increased transiently during the patient's convalescence. The cerebrospinal fluid/plasma ratios for branched-chain amino acids, α-keto acids, and α-hydroxy acids were very high before the transfurions and decreased after improvement. The cerebrospinal fluid/plasma rations for 5-carvon acids, α-ketoisovaleric acid and α-hydroxyisiovaleric acid were much higher than for other branched-chain acids not only in the patients but also in normal controls. Cerebrospinal fluid levels of α-ketoisocaproic acid and α-hydroxyisovaleric acid were as high as 1 mmol/l in our patient.