title: Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child.
abstract: BACKGROUND
  Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients' fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro.
  
  
  RESULTS
  A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient's growth pattern.
  
  
  CONCLUSIONS
  An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.
authors.affiliation: Unidade de Suprarrenal, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Candida Barisson Villares
authors.initials: MCBV
authors.lastname: Fragoso
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Edoarda Vasco de Albuquerque
authors.initials: EVA
authors.lastname: Albuquerque
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ana Luiza de Almeida
authors.initials: ALA
authors.lastname: Cardoso
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Paula Waki Lopes
authors.initials: PWL
authors.lastname: da Rosa
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo Bomeny
authors.initials: RB
authors.lastname: de Paulo
authors.affiliation: Laboratório de Pesquisa Básica em Doenças Renais LIM 12, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Heloisa Massola
authors.initials: MHM
authors.lastname: Schimizu
authors.affiliation: Laboratório de Pesquisa Básica em Doenças Renais LIM 12, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
authors.affiliation: Laboratório de Lípides (LIM 10) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Technische Universität, Dresden, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Koehler
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Technische Universität, Dresden, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.affiliation: Unidade de Suprarrenal, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.|Laboratório de Hormônios e Genética Molecular LIM 42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.|Laboratório de Hormônios e Genética Molecular LIM 42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ivo Jorge Prado
authors.initials: IJP
authors.lastname: Arnhold
authors.affiliation: Endocrinologia do Desenvolvimento, Divisão de Endocrinologia & Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.|Laboratório de Hormônios e Genética Molecular LIM 42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000309:Adrenal Insufficiency / Q000097:blood / Q000188:drug therapy*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004931:Esophageal Achalasia / Q000097:blood / Q000188:drug therapy*; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: Adrenal insufficiency; Allgrove syndrome; N-acetylcysteine; Thiobarbituric acid; Triple A syndrome