Molecular and Cellular Biochemistry

, Volume 402, Issue 1–2, pp 149–155 | Cite as

Increased oxidative stress in patients with 3-hydroxy-3-methylglutaric aciduria

  • Mariana dos Santos Mello
  • Graziela Schmitt Ribas
  • Carlos Alberto Yasin Wayhs
  • Tatiane Hammerschmidt
  • Gilian Batista Balbueno Guerreiro
  • Jéssica Lamberty Favenzani
  • Ângela Sitta
  • Daniella de Moura Coelho
  • Moacir Wajner
  • Carmen Regla Vargas


3-hydroxy-3-methylglutaric aciduria (HMGA; OMIM 246450) is a rare autosomal recessive disorder, caused by the deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (, which results in the accumulation of 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA) acids in tissues and biological fluids of affected individuals. Recent in vivo and in vitro animal studies have demonstrated that the accumulation of these metabolites can disturb the cellular redox homeostasis, which can contribute to the neurological manifestations presented by the patients. So, in the present work, we investigated oxidative stress parameters in plasma and urine samples from HMGA patients, obtained at the moment of diagnosis of this disorder and during therapy with low-protein diet and L-carnitine supplementation. It was verified that untreated HMGA patients presented higher levels of urinary di-tyrosine and plasma thiobarbituric acid-reactive substances (TBA-RS), which are markers of protein and lipid oxidative damage, respectively, as well as a reduction of the urinary antioxidant capacity. Treated HMGA patients also presented an increased protein oxidative damage, as demonstrated by their higher concentrations of plasma protein carbonyl groups and urinary di-tyrosine, as well as by the reduction of total sulfhydryl groups in plasma, in relation to controls. On the other hand, HMGA patients under therapy presented normal levels of TBA-RS and urinary antioxidant capacity, which can be related, at least in part, to the antioxidant and antiperoxidative effects exerted by L-carnitine. The results of this work are the first report showing that a redox imbalance occurs in patients with HMGA what reinforces the importance of the antioxidant therapy in this disorder.


3-hydroxy-3-methylglutaric aciduria Organic acidurias Carnitine Oxidative stress Oxidative damage 



The authors are grateful to the patients, their families, and the physicians of the patients. This work was supported in part by grants from CNPq, FAPERGS, and FIPE/HCPA-Brazil.

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mariana dos Santos Mello
    • 1
    • 2
  • Graziela Schmitt Ribas
    • 2
  • Carlos Alberto Yasin Wayhs
    • 2
  • Tatiane Hammerschmidt
    • 2
  • Gilian Batista Balbueno Guerreiro
    • 2
  • Jéssica Lamberty Favenzani
    • 2
  • Ângela Sitta
    • 2
  • Daniella de Moura Coelho
    • 2
  • Moacir Wajner
    • 2
    • 3
  • Carmen Regla Vargas
    • 1
    • 2
    • 3
  1. 1.Programa de Pós-Graduação Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Serviço de Genética Médica do Hospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil

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