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Review
. 2017 Sep 6:10:57-66.
doi: 10.2147/TACG.S125962. eCollection 2017.

Maple syrup urine disease: mechanisms and management

Patrick R Blackburn #  1   2 , Jennifer M Gass #  1 , Filippo Pinto E Vairo #  1   3 , Kristen M Farnham  4 , Herjot K Atwal  5 , Sarah Macklin  4 , Eric W Klee  1   3   4   6 , Paldeep S Atwal  1   4
Affiliations
Review

Maple syrup urine disease: mechanisms and management

Patrick R Blackburn et al. Appl Clin Genet. .

Abstract

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.

Keywords: BCKDHA; BCKDHB; DBT; alloisoleucine; branched-chain amino acids; maple syrup urine disease; newborn screening.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Overview of BCAA catabolic pathway. The BCAAs undergo transamination that is catalyzed by the branched-chain aminotransferase (BCAT) and requires α- ketoglutarate, leading to the production of the α-ketoacids KIC, KMV, and KIV. These intermediates then undergo oxidative decarboxylation, catalyzed by the BCKAD complex. Abbreviations: KIC, α-ketoisocaproic acid; KIV, α-ketoisovaleric acid; KMV, α-keto-β-methylvaleric acid; Glu, glutamate; BCAAs, branched-chain amino acids; BCKAD, branched-chain α-ketoacid dehydrogenase.
Figure 2
Figure 2
Overview of MSUD testing algorithm in NBS Abbreviations: BCAAs, branched-chain amino acids; MSUD, maple syrup urine disease; NBS, newborn screening
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