Oral L-alloisoleucine loading studies in healthy subjects and in patients with maple syrup urine disease

Abstract

Total body and renal elimination of L-alloisoleucine was assessed after oral loads (0.57 mmol/kg body wt) in four healthy subjects and in five patients with maple syrup urine disease (MSUD) of different degrees of severity. As judged from the fictive initial concentration, L-alloisoleucine is distributed evenly in the total body water space. In the controls, estimated half-time of total elimination was 9.2 +/- 2.2 h (n = 4). In the MSUD patients, it ranged from 26 h (mild variant) to about 8 d (classical type). Because of its low renal clearance rate, L-alloisoleucine was cleared through ketomethylvalerate to greater than 99% in normals and to at least 73% in the MSUD patients. Assuming small variation in the losses of ketomethylvalerate through L-isoleucine formation and through renal excretion, this test allows ranking of MSUD patients with regard to their residual in vivo branched-chain oxo-acid dehydrogenase activity.