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Maple syrup urine disease: mechanisms and management

Authors Blackburn PR, Gass JM, Vairo FP, Farnham KM, Atwal HK, Macklin S, Klee EW, Atwal PS

Received 1 June 2017

Accepted for publication 14 July 2017

Published 6 September 2017 Volume 2017:10 Pages 57—66

DOI https://doi.org/10.2147/TACG.S125962

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer


Patrick R Blackburn,1,2,* Jennifer M Gass,1,* Filippo Pinto e Vairo,3,4,* Kristen M Farnham,5 Herjot K Atwal,6 Sarah Macklin,5 Eric W Klee,3,4,7,8 Paldeep S Atwal1,5

1Center for Individualized Medicine, 2Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, 3Center for Individualized Medicine, 4Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 5Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, 6Department of Pharmacy, Mayo Clinic, Rochester, MN, 7Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, 8Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

*These authors contributed equally to this work

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

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