Urine odour maple syrup

Podebrad, F., Heil, M., Reichert, S., Mosandl, A., Sewell, A.C. and Bohles, H. (1999) 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone) - The odour of maple syrup urine disease. J. Inher. Metabol. Dis.22, 107-114. 

A similar success was observed for studies of branched-chain ketoaciduria in which the second stage of the catabolism of leucine, valine and isoleucine involves an oxidative decarboxylation. In patients with branched-chain ketoaciduria, this step is blocked for all three of these amino acids. The urine of these patients takes on the odour of maple syrup and hence this condition... 

MSUD is an autosomal recessive disorder caused by deficiency of branched-chain a-ketoacid dehydrogenase (Pig. 47.1). The a-ketoadds derived from isoleucine, valine and leucine (branched-chain amino adds) accumulate and are excreted in the urine, giving it the peculiar odour of maple syrup. The branched-chain amino acids and the branched-chain a-ketoacids that accumulate in the blood are neurotoxic, causing severe neurological symptoms, cerebral oedema and mental retardation. A diet low in branched-chain amino acids is an effective treafinenL... 

Another inherited error of valine, isoleucine and leucine metabolism is branched-chain a-keto aciduria, also known as maple syrup urine disease because the odour of urine of these patients resembles that of maple syrup. Branched-chain a-keto acid dehydrogenase, the enzyme complex that is used to oxidatively decarboxylate 2-ketoisovaleric, 2-keto-3-methylvaleric and 2-ketoisocaproic acids to the corresponding branched-chain CoA esters is defective, and very high concentrations of these keto acids accumulate in the blood and urine of these... 

A similar success was observed for studies of branched chain ketoaciduria in which the second stage of the catabolism of leucine, valine and isoleucine involves an oxidative decarboxylation. In patients with branched chain ketoaciduria, this step is blocked for all three of these amino acids. The urine of these patients takes on the odour of maple syrup and hence this condition is also known as maple syrup urine disease. H NMR spectroscopy was used to study the urines of patients with such branched chain ketoaciduria. The spectra showed several abnormal metabolites including the amino acids leucine, isoleucine and valine and their corresponding transamination products. It was noted that 2-hydroxyisovalerate levels were very high in the urines of all the patients studied and that, as in other inborn errors of metabolism, the levels of urinary glycine were elevated. 

As a consequence of the enzyme block, the three a-keto acids accumulate in the tissues and body fluids. The transamination step is reversible, hence the concentrations of leucine and isoleucine in the body fluids rise to about 10 to 15 times normal and that of valine to four to five times normal. The a-keto acids also undergo other reactions, including reduction to the O-hydroxy acids, some of the products being excreted and giving the urine the characteristic odour resembling maple syrup. 

---