Metabolic Brain Disease

, Volume 30, Issue 5, pp 1167–1174 | Cite as

Investigation of inflammatory profile in MSUD patients: benefit of L-carnitine supplementation

  • Caroline Paula MesckaEmail author
  • Gilian Guerreiro
  • Bruna Donida
  • Desirèe Marchetti
  • Carlos Alberto Yasin Wayhs
  • Graziela Schimitt Ribas
  • Adriana Simon Coitinho
  • Moacir Wajner
  • Carlos Severo Dutra-Filho
  • Carmen Regla Vargas
Research Article


Maple Syrup Urine Disease (MSUD) is a metabolic disorder caused by a severe deficiency of the branched-chain α-keto acid dehydrogenase complex activity which leads to the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine and valine and their respective α-keto-acids in body fluids. The main symptomatology presented by MSUD patients includes ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay and mental retardation, but, the neurological pathophysiologic mechanisms are poorly understood. The treatment consists of a low protein diet and a semi-synthetic formula restricted in BCAA and supplemented with essential amino acids. It was verified that MSUD patients present L-carnitine (L-car) deficiency and this compound has demonstrated an antioxidant and anti-inflammatory role in metabolic diseases. Since there are no studies in the literature reporting the inflammatory profile of MSUD patients and the L-car role on the inflammatory response in this disorder, the present study evaluates the effect of L-car supplementation on plasma inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-gamma (INF-ɣ), and a correlation with malondialdehyde (MDA), as a marker of oxidative damage, and with free L-car plasma levels in treated MSUD patients. Significant increases of IL-1β, IL-6, and INF-ɣ were observed before the treatment with L-car. Moreover, there is a negative correlation between all cytokines tested and L-car concentrations and a positive correlation among the MDA content and IL-1β and IL-6 values. Our data show that L-car supplementation can improve cellular defense against inflammation and oxidative stress in MSUD patients and may represent an additional therapeutic approach to the patients affected by this disease.


Maple syrup urine disease L-carnitine Inflammation Oxidative stress Antioxidant 



Maple syrup urine disease


Branched chain α-keto acid dehydrogenase


Branched-chain amino acid




Branched chain α-keto acids


α-ketoisocaproic acid







IFN -ɣ





Reactive oxygen species



Very special thanks are dedicated to the physicians at the Medical Genetic Service of Hospital de Clinicas de Porto Alegre, families and patients who participated in this study. This work was supported in part by grants from FAPERGS, CNPq and FIPE/HCPA-Brazil.

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Caroline Paula Mescka
    • 2
    • 3
    Email author
  • Gilian Guerreiro
    • 2
    • 4
  • Bruna Donida
    • 2
    • 3
  • Desirèe Marchetti
    • 2
    • 3
  • Carlos Alberto Yasin Wayhs
    • 2
    • 4
  • Graziela Schimitt Ribas
    • 2
  • Adriana Simon Coitinho
    • 5
  • Moacir Wajner
    • 2
    • 3
  • Carlos Severo Dutra-Filho
    • 3
  • Carmen Regla Vargas
    • 1
    • 2
    • 3
    • 4
  1. 1.Faculdade de FarmáciaUFRGSPorto AlegreBrazil
  2. 2.Serviço de Genética Médica, HCPAUFRGSPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em CB:BioquímicaUFRGSPorto AlegreBrazil
  4. 4.Programa de Pós-Graduação em Ciências FarmacêuticasUFRGSPorto AlegreBrazil
  5. 5.Programa de Pós-Graduação em CB:FisiologiaUFRGSPorto AlegreBrazil

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