Maple syrup urine disease (MSUD), also known as branched-chain ketoaciduria, is an aminoacidopathy due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding alpha-keto acids leads to encephalopathy and progressive neurodegeneration in untreated infants. Early diagnosis and dietary intervention prevent complications and may allow for normal intellectual development. Consequently, maple syrup urine disease has been added to many newborn screening programs, and preliminary results indicate that asymptomatic newborns with maple syrup urine disease have better outcomes compared with infants who are diagnosed after they become symptomatic.

In 1954, Menkes et al reported a family in which 4 infants died within the first 3 months of life owing to a neurodegenerative disorder. The urine of these infants had an odor similar to that of maple syrup (burnt sugar). [1] Therefore, this disorder was called maple sugar urine disease and, later, maple syrup urine disease. In the following years, Dancis et al identified the pathogenetic compounds as branched-chain amino acids and their corresponding alpha-keto acids. [2] In 1960, Dancis et al demonstrated that the enzymatic defect in maple syrup urine disease was at the level of the decarboxylation of the branched-chain amino acids. [3] Snyderman et al initiated the first successful dietary treatment of maple syrup urine disease by restricting oral intake of branched-chain amino acids. [4] In 1971, Scriver et al reported the first case of thiamine-responsive maple syrup urine disease. [5] The branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex was purified and characterized in 1978. [2]