Cited by 280Metabolism and Genetic DisordersAmino Acid Enzymes and MetabolismBiochemical Acid Research Studies

The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.

Maple syrup urine disease: mechanisms and management

Open access

Blackburn, Patrick, Gass, Jennifer, Pinto e Vairo, Filippo, Farnham, Kristen, Atwal, Herjot, Macklin, Sarah, Klee, Eric, Atwal, Paldeep·2017·The Application of Clinical Genetics

DOI 10.2147/tacg.s125962PMC PMC5593394

Open this paper in CoChat — free account Open PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.2147/tacg.s125962

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

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.CC BY-NC · PubMed Central

Figure 2 Overview of MSUD testing algorithm in NBS Abbreviations: BCAAs, branched-chain amino acids; MSUD, maple syrup urine disease; NBS, newborn screeningCC BY-NC · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Branched-chain amino acids in metabolic signalling and insulin resistance
Lynch, C. J., & Adams, S. H. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.171 · Cited by 1,461
Branched-Chain Amino Acid Metabolism
Harper, A. E., Miller, R. H., & Block, K. P. (1984) · Annual Review of Nutrition · doi:10.1146/annurev.nu.04.070184.002205 · Cited by 1,011
Branched-Chain Amino Acid Metabolism
Yudkoff, M. (1999) · Cited by 762
Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns
Chace, D. H., Kalas, T. A., & Naylor, E. W. (2003) · Clinical Chemistry · doi:10.1373/clinchem.2003.022178 · Cited by 621
Current status of newborn screening worldwide: 2015
Therrell, B. L., Padilla, C. D., Loeber, J. G., Kneisser, I., Saadallah, A., Borrajo, G. J. C., & Adams, J. (2015) · Seminars in Perinatology · doi:10.1053/j.semperi.2015.03.002 · Cited by 602
Branched-Chain Amino Acids: Enzyme and Substrate Regulation
Brosnan, J. T., & Brosnan, M. E. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.1.207s · Cited by 577
Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus.
Wahren, J., Felig, P., & Hagenfeldt, L. (1976) · Journal of Clinical Investigation · doi:10.1172/jci108375 · Cited by 369
Diagnosis and Treatment of Maple Syrup Disease: A Study of 36 Patients
Morton, D. H., Strauss, K. A., Robinson, D. L., Puffenberger, E. G., & Kelley, R. I. (2002) · PEDIATRICS · doi:10.1542/peds.109.6.999 · Cited by 325
Maple syrup urine disease (branched-chain ketoaciduria)
Chuang, D. (2001) · Medical Entomology and Zoology · Cited by 243
Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry
Chace, D. H., Hillman, S. L., Millington, D. S., Kahler, S. G., Roe, C. R., & Naylor, E. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.1.62 · Cited by 219
Brain Amino Acid Requirements and Toxicity: The Example of Leucine
Yudkoff, M., Daikhin, Y., Nissim, I. B., Horyn, O., Luhovyy, B. L., Lazarow, A., & Nissim, I. (2005) · Journal of Nutrition · doi:10.1093/jn/135.6.1531s · Cited by 196
Nutrition management guideline for maple syrup urine disease: An evidence- and consensus-based approach
Frazier, D. M., Allgeier, C., Homer, C., Marriage, B. J., Ogata, B., Rohr, F., Splett, P. L., Stembridge, A., & Singh, R. H. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.05.006 · Cited by 196
Classical maple syrup urine disease and brain development: Principles of management and formula design
Strauss, K. A., Wardley, B. L., Robinson, D., Hendrickson, C. L., Rider, N. L., Puffenberger, E. G., Shelmer, D., Moser, A. B., & Morton, D. H. (2009) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.12.007 · Cited by 195
Liver Transplantation for Classical Maple Syrup Urine Disease: Long-Term Follow-Up in 37 Patients and Comparative United Network for Organ Sharing Experience
Mazariegos, G. V., Morton, D. H., Sindhi, R. K., Soltys, K. A., Nayyar, N. S., Bond, G., Shellmer, D. A., Shneider, B. L., Vockley, J. E., & Strauss, K. A. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.06.033 · Cited by 184
THIAMINE-RESPONSIVE MAPLE-SYRUP-URINE DISEASE
Scriver, C. R., Clow, C., Mackenzie, S., & DELVIN, E. E. (1971) · The Lancet · doi:10.1016/s0140-6736(71)91041-5 · Cited by 173
Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders
Burrage, L. C., Nagamani, S. C. S., Campeau, P. M., & Lee, B. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu123 · Cited by 147
Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease
Strauss, K. A., Mazariegos, G. V., Sindhi, R. K., Squires, R., Finegold, D. N., Vockley, J. E., Robinson, D. L., Hendrickson, C., Virji, M. A., Cropcho, L. J., et al. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.01209.x · Cited by 129
Second-Tier Test for Quantification of Alloisoleucine and Branched-Chain Amino Acids in Dried Blood Spots to Improve Newborn Screening for Maple Syrup Urine Disease (MSUD)
Oglesbee, D., Sanders, K. A., Lacey, J. M., Magera, M. J., Casetta, B., Strauss, K. A., Tortorelli, S., Rinaldo, P., & Matern, D. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2007.098434 · Cited by 128
Astrocyte Leucine Metabolism: Significance of Branched‐Chain Amino Acid Transamination
Yudkoff, M., Daikhin, Y., Grunstein, L., Nissim, I. B., Stern, J., Pleasure, D., & Nissim, I. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66010378.x · Cited by 121
Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice
Joshi, M., Jeoung, N. H., Obayashi, M., Hattab, E. M., Brocken, E., Liechty, E. A., Kubek, M. J., Vattem, K. M., Wek, R. C., & Harris, R. A. (2006) · Biochemical Journal · doi:10.1042/bj20060869 · Cited by 118
Biochemical correlates of neuropsychiatric illness in maple syrup urine disease
Muelly, E. R., Moore, G. J., Bunce, S. C., Mack, J. A., Bigler, D. C., Morton, D. H., & Strauss, K. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67217 · Cited by 117
Interrelationships of Leucine and Glutamate Metabolism in Cultured Astrocytes
Yudkoff, M., Daikhin, Y., Lin, Z., Nissim, L., Stern, J., Pleasure, D., & Nissim, I. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62031192.x · Cited by 97
Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders
Burrage, L. C., Jain, M., Gandolfo, L., Lee, B., & Nagamani, S. C. S. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.06.005 · Cited by 75
Newborn Screening for Maple Syrup Urine Disease (Branched-Chain Ketoaciduria)
Naylor, E. (1980) · Springer eBooks · doi:10.1007/978-3-642-67488-4_3 · Cited by 73
Branched-chain ketoacyl dehydrogenase deficiency: Maple syrup disease
Strauss, K. A., & Morton, D. H. (2003) · Current Treatment Options in Neurology · doi:10.1007/s11940-003-0039-3 · Cited by 70
Maple syrup urine disease: Further evidence that newborn screening may fail to identify variant forms
Puckett, R. L., Lorey, F., Rinaldo, P., Lipson, M. H., Matern, D., Sowa, M., Levine, S., Chang, R. C., Wang, R. Y., & Abdenur, J. E. (2009) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.11.010 · Cited by 63
Branched-Chain Amino Acid Metabolism
Harper, A. E. (1984) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.4.1.409 · Cited by 63
Newborn Screening for Maple Syrup Urine Disease (Branched-Chain Ketoaciduria)
Naylor, E. W., & Guthrie, R. W. (1978) · PEDIATRICS · doi:10.1542/peds.61.2.262 · Cited by 62
CONGENITAL LACTIC ACIDOSIS, α‐KETOGLUTARIC ACIDURIA AND VARIANT FORM OF MAPLE SYRUP URINE DISEASE DUE TO A SINGLE ENZYME DEFECT: DIHYDROLIPOYL DEHYDROGENASE DEFICIENCY
Münnich, A., Saudubray, J., Taylor, J. P., Charpentier, C., Marsac, C., Rocchiccioli, F., Amédée-Manesme, O., Coudé, F. X., Frézal, J., & Robinson, B. H. (1982) · Acta Paediatrica · doi:10.1111/j.1651-2227.1982.tb09393.x · Cited by 60
Dihydrolipoamide dehydrogenase deficiency: A still overlooked cause of recurrent acute liver failure and Reye-like syndrome
Brassier, A., Ottolenghi, C., Boutron, A., Bertrand, A.-M., Valmary‐Degano, S., Cervoni, J., Chrétien, D., Arnoux, J., Hubert, L., Rabier, D., et al. (2013) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2013.01.017 · Cited by 57
Acute illness in maple syrup urine disease: Dynamics of protein metabolism and implications for management
Thompson, G. N., Francis, D., & Halliday, D. (1991) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)81035-2 · Cited by 52
Movement disorders in adult surviving patients with maple syrup urine disease
Carecchio, M., Schneider, S. A., Chan, H., Lachmann, R., Lee, P., Murphy, E., & Bhatia, K. P. (2011) · Movement Disorders · doi:10.1002/mds.23629 · Cited by 48
BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice
Lang, C. H., Lynch, C. J., & Vary, T. C. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00297.2010 · Cited by 47
Leigh Syndrome in a Girl With a Novel DLD Mutation Causing E3 Deficiency
Quinonez, S. C., Leber, S. M., Martin, D. M., Thoene, J. G., & Bedoyan, J. K. (2013) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2012.09.013 · Cited by 45
Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis
Couce, M. L., Ramos, F. J., Bueno, M. A., Díaz, J. J., Meavilla, S. M., Boveda, M. D., Marmiesse, A. F., & García‐Cazorla, À. (2015) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2015.07.009 · Cited by 40
The adolescent with an inborn error of metabolism: medical issues and transition to adulthood.
Enns, G. M., & Packman, W. L. (2002) · PubMed · Cited by 36
Living related versus deceased donor liver transplantation for maple syrup urine disease
Feier, F. H., Schwartz, I. V. D., Benkert, A. R., Neto, J. S., Miura, I. K., Chapchap, P., da Fonseca, E. A., Vieira, S. M. G., Zanotelli, M. L., Vairo, F. P. E., et al. (2016) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2016.01.005 · Cited by 36
Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy
Zinnanti, W. J., & Lazović, J. (2011) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-011-9333-5 · Cited by 32
GENETIC SCREENING: Carriers and Affected Individuals
McCabe, L. L., & McCabe, E. R. B. (2004) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.5.061903.175941 · Cited by 30
Young Adults with MSUD and Their Transition to Adulthood: Psychosocial Issues
Packman, W. L., Mehta, I., Rafie, S., Mehta, J., Naldi, M., & Mooney, K. H. (2012) · Journal of Genetic Counseling · doi:10.1007/s10897-012-9490-1 · Cited by 29
Cerebral edema in maple syrup urine disease
Levin, M. L., Scheimann, A., Lewis, R. A., & Beaudet, A. L. (1993) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)83521-8 · Cited by 29
Serum Markers of Neurodegeneration in Maple Syrup Urine Disease
Scaini, G., Tonon, T., de Souza, C. F. M., Schuk, P. F., Ferreira, G. C., Neto, J. S., Amorin, T., Schwartz, I. V. D., & STRECK, E. L. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0116-8 · Cited by 27
Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases
Li, X., Ding, Y., Liu, Y., Ma, Y., Song, J., Wang, Q., Li, M., Qin, Y., & Yang, Y. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.10.002 · Cited by 26
Brain–blood amino acid correlates following protein restriction in murine maple syrup urine disease
Vogel, K. R., Arning, E., Wasek, B. L., McPherson, S., Bottiglieri, T., & Gibson, K. M. (2014) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-9-73 · Cited by 25
Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease
Imtiaz, F., Al‐Mostafa, A., Allam, R., Ramzan, K., Tassan, N. A. A., Tahir, A. I., Al‐Numair, N. S., Al‐Hamed, M. H., Al‐Hassnan, Z. N., Al-Owain, M., et al. (2017) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2017.03.006 · Cited by 23
Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino‐acid mixture
Servais, A., Arnoux, J., Lamy, C., Hummel, A., Vittoz, N., Katerinis, I., Bazzaoui, V., Dubois, S., Broissand, C., Husson, M., et al. (2012) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-012-9570-2 · Cited by 21
In silico analysis of novel mutations in maple syrup urine disease patients from Iran
Abiri, M., Karamzadeh, R., Mojbafan, M., Alaei, M. R., Jodaki, A., Safi, M., Kianfar, S., Sarhaddi, A. B., Noori–Daloii, M. R., Karimipoor, M., et al. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9867-1 · Cited by 20
Management of a Woman With Maple Syrup Urine Disease During Pregnancy, Delivery, and Lactation
Wessel, A. E., Mogensen, K. M., Rohr, F., Erick, M. A., Neilan, E. G., Chopra, S., Levy, H. L., Gray, K. J., Wilkins-Haug, L. E., & Berry, G. T. (2014) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607114526451 · Cited by 18
Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease
Atwal, P. S., Macmurdo, C., & Grimm, P. C. (2015) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2015.07.001 · Cited by 14
Self-citation
Wernicke‐like encephalopathy during classic maple syrup urine disease decompensation
Manara, R., Rizzo, M. D., Burlina, A. P., Bordugo, A., Citton, V., Rodríguez‐Pombo, P., Ugarte, M., & Burlina, A. (2012) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-012-9456-3 · Cited by 11
Nutrition Management of Maple Syrup Urine Disease
van Calcar, S. (2015) · Springer eBooks · doi:10.1007/978-3-319-14621-8_16 · Cited by 9
cDNA Cloning of the E1α Subunit of the Branshed‐Chain α‐Keto Acid Dehydrogenase and Elucidation of a Molecular Basis for Maple Syrup Urine Diseasea
ZHANG, B., Kuntz, M. J., Goodwin, G. W., Edenberg, H. J., Crabb, D. W., & Harris, R. A. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb14991.x · Cited by 9

Research works printed but not linked: 1

[50]Strauss KA Wardley B Robinson D Classical maple syrup urine disease and brain development: Principles of management and formula design Mol Genet Metab 2010 99 4 333 345 20061171 PMC3671925

Sorted by citations

The multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935
Emerging Roles for Branched-Chain Amino Acid Metabolism in Cancer
Sivanand, S., & Heiden, M. G. V. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.011 · Cited by 498
Branched-chain amino acids in cardiovascular disease
McGarrah, R. W., & White, P. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00760-3 · Cited by 296
Semisynthetic sensor proteins enable metabolic assays at the point of care
Yu, Q., Xue, L., Hiblot, J., Griss, R., Fabritz, S., Roux, C., Binz, P., Haas, D., Okun, J. G., & Johnsson, K. (2018) · Science · doi:10.1126/science.aat7992 · Cited by 159
Recent Progress on Branched-Chain Amino Acids in Obesity, Diabetes, and Beyond
Siddik, M. A. B., & Shin, A. C. (2019) · Endocrinology and Metabolism · doi:10.3803/enm.2019.34.3.234 · Cited by 137

See all 280

Authors: Blackburn, P., Gass, J., Pinto e Vairo, F., Farnham, K., Atwal, H., Macklin, S., Klee, E., & Atwal, P.
Affiliations: Mayo Clinic in Florida (US)
Mayo Clinic (US)
Corresponding author: Atwal, Paldeep
ORCID: Gass, Jennifer
Macklin, Sarah
Klee, Eric
Atwal, Paldeep
Venue: The Application of Clinical Genetics
Publisher: Informa UK Limited
Published: 2017-09
Volume: Volume 10
Pages: 57-66
ISSN: 1178-704X (ISSN-L)
DOI: 10.2147/tacg.s125962
PMC: PMC5593394
OpenAlex: W2752428554
Cited by: 280
References: 53
Citations by year: 2026: 26 · 2025: 38 · 2024: 55 · 2023: 32 · 2022: 31 · 2021: 42 · 2020: 27 · 2019: 17 · 2018: 10
FWCI: 1.93
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/3.0/ (unspecified)
Locations: The Application of Clinical Genetics (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders: Mayo Clinic
Center for Individualized Medicine, Mayo Clinic
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords: maple syrup urine disease, branched-chain amino acids, inborn errors of metabolism, alloisoleucine, clinical variants, neonatal presentation, neurological complications, dietary restriction, metabolic monitoring, newborn screening

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Maple syrup urine disease: mechanisms and management

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks