title: Metabolic characterisation of plasma in juveniles with glycogen storage disease type 1a (GSD1a) by high-resolution (1)H NMR spectroscopy.
abstract: This paper reports the first application of high-resolution (1)H NMR spectroscopy to the plasma of five juveniles with glycogen storage disease type 1a (GSD1a), permitting the characterisation of the plasma metabolic profile and the identification of alterations relative to a set of control samples. The relaxation-weighted spectra allowed changes in low molecular weight compounds to be detected more clearly, whereas diffusion-edited spectra were used to characterise the plasma lipoprotein profile. Low molecular weight metabolites with altered levels in most patients were lactate, ketone bodies, acetate, creatine/creatinine and glucose. One of the patients showed distinctively lower glucose levels and higher lactate and ketone body contents, suggesting poorer metabolic control of the disease compared with other patients. In addition, a metabolite tentatively identified as alpha-hydroxyisobutyrate was only detected in the spectra of GSD1a plasmas, representing, therefore, a possible novel GSD1a biomarker. Total lipoprotein contents were higher in the plasma from GSD1a patients. Furthermore, lower HDL and higher VLDL + LDL levels also characterised the plasma of these patients. Preliminary results on principal component analysis of (1)H NMR spectra allowed a clear separation between GSD1a and control plasmas. The specificity of the changes observed to GSD1a is discussed, together with the recognised potential of NMR and pattern recognition methods for aiding the diagnosis of GSD1a.
authors.affiliation: CICECO, Department of Chemistry, Campus Universitário de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal. ioladuarte@dq.ua.pt
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: António
authors.initials: A
authors.lastname: Barros
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
authors.forename: Cristina
authors.initials: C
authors.lastname: Barosa
authors.forename: Luisa
authors.initials: L
authors.lastname: Diogo
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D005260:Female; D005953:Glycogen Storage Disease Type I / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D006885:Hydroxybutyrates; D008074:Lipoproteins; C031570:2-hydroxybutyric acid