Archives of Disease in Childhood · 1963 · 69 citations · 13 references
Maple syrup urine disease is one of a number of cerebro-degenerative conditions, which is caused, directly or indirectly, by a congenital defect in amino acid metabolism. However, in contrast to other diseases of a similar type, notably phenylketonuria, the affected children frequently die within the first month and the survivors rarely live for longer than two years (Menkes, Hurst and Craig, 1954). In 1957, Westall, Dancis and Miller reported that in this disease the blood and urine contained excessive amounts ofleucine, isoleucine, valine and methionine. This has since been confirmed in other cases, and it was further reported that the keto and hydroxy acid analogues of these amino acids were also present in the urine Recently Norton, Roitman, Snyderman and Holt (1962) have shown that methionine was implicated incorrectly through an analytical error. It so happened that the methionine peak on the flow sheet obtained by the Moore and Stein (1954) ion-exchange column method for amino acid analysis was exactly superimposed on a peak due to an unidentified substance. Norton et al. (1962) using a modification of the above method (Piez and Morris, 1960) have separated the two substances and tentatively identified the unknown as alloisoleucine, a substance which hitherto had not been found in body fluids. This simplifies our biochemical con- cepts of the disease, as alloisoleucine is clearly more closely related to the other three branched-chain amino acids than is methionine.
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