William J. Zinnanti1, Jelena Lazovic2, John Flanagan3
1Biochemistry, Pennsylvania State University, Hershey, PA, USA; 2Biology, California Institute of Technology, Pasadena, CA, USA; 3Biochemistry, Pennsulvania State University, Hershey, PA, USA
Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid (BCAA) metabolism that requires life-long leucine restriction and monitoring. Despite strict diet adherence, children with MSUD commonly suffer encephalopathy associated with catabolic stress of non-specific childhood illnesses. Encephalopathy may involve accumulation of brain leucine and usually results in life-threatening cerebral edema and death. Using a recently developed mouse model of MSUD, we show development of brain damage after induction of encephalopathy with a high-protein diet. Administration of 5% norleucine reduces brain leucine accumulation, delays encephalopathy and enhances survival of MSUD mice.