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Sci Rep. 2018 Feb 14;8(1):2977. doi: 10.1038/s41598-018-20834-y.

Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism.

Author information

1
Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, BO, Italy.
2
CERM, Center of Magnetic Resonance, University of Florence, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.
3
CIRMMP, Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.
4
Neonatology Unit, St. Orsola-Malpighi Polyclinic, Via Massarenti 9, 40138, Bologna, BO, Italy.
5
Neonatology Unit, St. Orsola-Malpighi Polyclinic, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, BO, Italy.
6
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Via Amendola 165/A, I-70126, Bari, Italy.
7
Department of Medical and Biological Sciences, University of Udine, P.le Massimiliano Kolbe 4, 33100, Udine, Italy.
8
Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Florence, Italy.
9
Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, BO, Italy. pierluigi.strippoli@unibo.it.

Abstract

Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to of 80% accuracy) between the DS and the control groups. The univariate analysis of plasma and urine revealed a significant alteration for some interesting metabolites. Remarkably, most of the altered concentrations were consistent with the 3:2 gene dosage model, suggesting effects caused by the presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was 1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4 (formate). Several significantly altered metabolites are produced at the beginning or during the Krebs cycle. Accounting for sex, age and fasting state did not significantly affect the main result of both multivariate and univariate analysis.

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