CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological artefacts

Abstract:

McGregor et al. reported increased levels of an unidentified urinary compound (CFSUM1) in patients with chronic fatigue syndrome (CFS), with reduced excretion of another unidentified compound (CFSUM2), and suggested the possibility of chemical or metabolic ‘markers’ for CFS. The identity of CFSUM1 as reported was erroneous and the identities of these compounds have remained unknown until now.

Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched healthy controls, 20 control patients with depression and 22 control patients with rheumatoid arthritis. Samples were prepared using the published methods of McGregor et al. to produce heptafluorobutyryl-isobutyl derivatives of urinary metabolites. Alternative preparations utilised isopropyl, n-butyl and trifluoroacetyl derivatives. These were separated and identified using gas chromatography-mass spectrometry.

CFSUM2 was identified as being partially derivatised [isobutyl ester-mono-heptafluorobutyryl (HFB)] serine. CFSUM1 was identified as partially derivatised pyroglutamic acid, being the isobutyl ester without formation of a HFB derivative.

Both CFSUM1 and CFSUM2 are artefacts of the sample preparation procedure and previously reported quantitative abnormalities of CFSUM1 and CFSUM2 in urine from patients with ME/CFS are also artefactual. Pyroglutamic acid may be of primarily dietary origin. The methods used cannot provide reliable qualitative or quantitative data on urinary metabolites. No clinical or biochemical significance can be drawn between these compounds in ME/CFS or any other clinical conditions.

 

Source: Chalmers RA, Jones MG, Goodwin CS, Amjad S. CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological artefacts. Clin Chim Acta. 2006 Feb;364(1-2):148-58. Epub 2005 Aug 10. http://www.ncbi.nlm.nih.gov/pubmed/16095585

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

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.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884