title: Profiles of amino acids and biogenic amines in the plasma of Cri-du-Chat patients.
abstract: Cri-du-chat syndrome (CDCS) is a rare innate disease attributed to chromosome 5p deletion characterized by a cat-like cry, craniofacial malformation, and altered behavior of affected children. Metabolomic analysis and a chemometric approach allow description of the metabolic profile of CDCS as compared to normal subjects. In the present work, UHPLC/MS was employed to analyze blood samples withdrawn from CDCS carriers (n=18) and normal parental subjects (n=18), all aged 0-34 years, aiming to set up a representative CDCS profile constructed from 33 targeted amino acids and biogenic amines. Methionine sulfoxide (MetO) was of particular concern with respect to CDCS redox balance. Increased serotonin (3-fold), methionine sulfoxide (2-fold), and Asp levels, and a little lower Orn, citrulline, Leu, Val, Ile, Asn, Gln, Trp, Thr, His, Phe, Met, and creatinine levels were found in the plasma of CDCS patients. Nitrotyrosine and Trp did not differ in normal and CDCS individuals.The accumulated metabolites may reflect, respectively, disturbances in the redox balance, deficient purine biosynthesis, and altered behavior, whereas the amino acid abatement in the latter group may affect the homeostasis of the urea cycle, citric acid cycle, branched chain amino acid synthesis, Tyr and Trp metabolism and amino acid biosynthesis. The identification of enzymatic deficiencies leading to the amino acid burden in CDCS is further required for elucidating its molecular bases and eventually propose specific or mixed amino acid supplementation to newborn patients aiming to balance their metabolism.
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Danielle Zildeana Sousa
authors.initials: DZS
authors.lastname: Furtado
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Fernando Brunale Vilela
authors.initials: FBV
authors.lastname: de Moura Leite
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Cleber Nunes
authors.initials: CN
authors.lastname: Barreto
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Bernadete
authors.initials: B
authors.lastname: Faria
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Leticia Dias Lima
authors.initials: LDL
authors.lastname: Jedlicka
authors.affiliation: A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
authors.forename: Elisângela
authors.initials: E
authors.lastname: de Jesus Silva
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil.
authors.forename: Heron Dominguez Torres
authors.initials: HDT
authors.lastname: da Silva
authors.affiliation: Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Etelvino Jose Henriques
authors.initials: EJH
authors.lastname: Bechara
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP, Brazil. Electronic address: nilson.assuncao@gmail.com.
authors.forename: Nilson Antonio
authors.initials: NA
authors.lastname: Assunção
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D001679:Biogenic Amines; D003410:Cri-du-Chat Syndrome; D006801:Humans; D010446:Peptide Fragments
chemical_list: D000596:Amino Acids; D001679:Biogenic Amines; D010446:Peptide Fragments
keywords: Amino acids; Biogenic amines; Chemometrics; Chromosome 5; Mass spectrometry