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Overview of maple syrup urine disease

Olaf A Bodamer, MD, PhD, FAAP, FACMG
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Maple syrup urine disease (MSUD, MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids. It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three branched-chain amino acids, leucine, isoleucine, and valine. It is characterized by psychomotor delay, feeding problems, and a maple syrup odor of the urine.

MSUD is reviewed here. A general discussion of amino acid disorders is presented separately. (See "Inborn errors of metabolism: Classification".)


MSUD occurs in approximately 1 in 86,800 to 185,000 live births [1-3]. It occurs more frequently in populations with an increased frequency of consanguinity, such as the Mennonites in Pennsylvania, where the incidence is as high as 1 in 200 births [4].


The branched-chain amino acids, leucine, isoleucine, and valine, are essential amino acids with hydrophobic side chains and are important precursors for gluconeogenesis, energy production, and synthesis of fatty acids and cholesterol [5].

In the first step of branched-chain metabolism, branched-chain amino acids are converted by cytosolic and mitochondrial branched-chain aminotransferases (BCATs) to their respective alpha-ketoacids. The alpha-ketoacids are subsequently decarboxylated by the branched-chain ketoacid dehydrogenase complex (BCKDC) to yield isovaleryl-coenzyme A (CoA), alpha-methylbutyryl-CoA, and isobutyrl-CoA, respectively, which eventually result in acetyl-CoA, acetoacetate, and succinyl-CoA (figure 1) [5,6].

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Literature review current through: Nov 2017. | This topic last updated: Aug 16, 2016.
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