Studies in maple syrup urine disease.

Menkes, Hurst and Craig (1954) described four infants with a progressive cerebro-degenerative disease. They were from a family of six children. Two were quite normal and of the four affected infants one survived for three months, but the others died within 14 days. An outstanding characteristic of the disease was the peculiarly pleasant smell of the urine, which was similar to that of maple syrup. Westall, Dancis and Miller (1957) reported a further clinically similar case which had survived until 20 months old. They found that the urine, which had the same characteristic odour, also contained excessive amounts of leucine, isoleucine and valine. Examination of the blood plasma revealed excessively high levels of these amino acids and also of methionine whilst the other amino acids were normal or at subnormal levels. Meanwhile, Menkes (1959) and Dancis, Levitz, Miller and Westall (1959), working on the urine from the same case, reported an elevated excretion of the branched-chain keto acids corresponding to the deaminated amino acids leucine, isoleucine and valine. Concurrently, Mackenzie and Woolf (1959), who had discovered a new case, confirmed the aminoacidaemia and aminoaciduria for the branched-chain amino acids and also independently discovered the excessive excretion of the corresponding keto acids. In 1959, the case described by Mackenzie and Woolf, which had been admitted to The Hospital for Sick Children, Great Ormond Street, under Professor A. Moncrieff, was transferred for further studies to the Metabolic Ward of University College Hospital under the care of one of us (C.E.D.).