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

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.