Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation

We characterized the effect of orthotopic liver transplantation on the catabolism of branched-chain L-amino acids in a female patient with classical form of maple syrup urine disease. Transplantation was performed at the age of 7.4 years due to a terminal liver failure triggered by a hepatitis A infection. Since then, the patient is on an unrestricted diet and plasma concentrations of branched-chain L-amino and 2-oxo acids are stable, yet at moderately increased levels (2- to 3-fold of control). L-Alloisoleucine concentrations, however, remained remarkably elevated (>5-fold of control). In vivo catabolism was investigated by measuring the metabolic L-alloisoleucine clearance and whole-body leucine oxidation in the postabsorptive state. In an oral loading test with 580 mu mol alloisoleucine per kg body wt, the L-alloisoleucine elimination rate constant (0.067 h(-1)) was in the normal range (0.069 +/-0.012 h(-1), n=4). In an oral L-[1-C-13]leucine load (38 mu mol/kg body wt), 19.5% of the tracer dose applied was recovered in exhaled (CO2)-C-13 versus 18.9 +/-3.6% in healthy subjects (n=10). Thus, the patient exhibited obviously normal whole-body catabolic rates although branched-chain L-amino acid oxidation was confined to the liver transplant. Most likely, the enhanced substrate supply from extrahepatic sources led to an elevation of the plasma concentrations and thus induced a compensatory enhancement of the metabolic flux through the branched-chain 2-oxo acid dehydrogenase complex in the intact liver tissue.