Preliminary determination of a molecular basis of chronic fatigue syndrome.
Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects. Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion. Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects. The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.
McGregor
N R
NR
Collaborative Pain Research Unit, University of Sydney, Westmead Hospital, NSW, Australia.
Dunstan
R H
RH
Zerbes
M
M
Butt
H L
HL
Roberts
T K
TK
Klineberg
I J
IJ
D000156:Aconitic Acid / Q000652:urine; D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000652:urine; D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine; D015673:Fatigue Syndrome, Chronic / Q000503:physiopathology / Q000523:psychology / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D018698:Glutamic Acid / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010808:Physical Examination; D011759:Pyrrolidines / Q000652:urine; D012016:Reference Values; D013386:Succinates / Q000652:urine; D019802:Succinic Acid; D011795:Surveys and Questionnaires; D014443:Tyrosine / Q000652:urine; D015091:beta-Alanine / Q000652:urine
C103601:3-amino-1-methylpyrrolidin-2-ol; D000596:Amino Acids; D015415:Biomarkers; D011759:Pyrrolidines; D013386:Succinates; D015091:beta-Alanine; D018698:Glutamic Acid; D014443:Tyrosine; D000156:Aconitic Acid; D019802:Succinic Acid; D000409:Alanine