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Serum Markers of Neurodegeneration in Maple Syrup Urine Disease

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An Erratum to this article was published on 04 November 2016

This article has been updated

Abstract

Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.

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  • 04 November 2016

    An erratum to this article has been published.

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Acknowledgments

Laboratory of Bioenergetics (Brazil) is one of the centers of the National Institute for Molecular Medicine (INCT-MM) and one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq (402047/2010-9), FAPESC, and UNESC. The authors acknowledge all the members of the Brazilian MSUD Network and Dr. Kevin Strauss and Dr. Erik Puffenberger (Clinical for Special Children, PA, USA) for helping us with the alloisoleucine measurement. The authors declare that they have not had any financial, personal, or other relationships that have influenced the work.

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Authors and Affiliations

  1. Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil

    Giselli Scaini & Emilio L. Streck

  2. Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Tássia Tonon & Ida Vanessa D. Schwartz

  3. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Carolina F. Moura de Souza & Ida Vanessa D. Schwartz

  4. Laboratório de Erros Inatos do Metabolismo, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Patricia F. Schuk

  5. Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Gustavo C. Ferreira

  6. Hospital Sirio Libanes, São Paulo, Brazil

    Joao Seda Neto

  7. Associação de Pais e Amigos dos Excepcionais (APAE), Salvador, Brazil

    Tatiana Amorin

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  1. Giselli Scaini
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  2. Tássia Tonon
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  9. Emilio L. Streck
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Correspondence to Emilio L. Streck.

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The present study was approved by the Ethical Committee of Hospital de Clínicas de Porto Alegre, RS, Brazil. All parents of the patients included in the present study provided informed consent according to the guidelines of our committee.

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An erratum to this article is available at https://doi.org/10.1007/s12035-016-0263-y.

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Scaini, G., Tonon, T., de Souza, C.F.M. et al. Serum Markers of Neurodegeneration in Maple Syrup Urine Disease. Mol Neurobiol 54, 5709–5719 (2017). https://doi.org/10.1007/s12035-016-0116-8

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