Dunstan RH, McGregor NR, Butt HL, Roberts TK, Zerbes M, Klineberg IJ*.
Collaborative Pain Research Unit
Department of Biological Sciences
The University of Newcastle
Callaghan, NSW 2308
* Neurobiology Research Unit
Centre for Oral Health Research
University of Sydney
Westmead, NSW 2084
Homeostatic Heterogeneity in CFS Patients
The original definition of CFS published by the American Centres for Disease Control (CDC) was initially conceived to treat CFS as a potentially infectious disease as evidenced by the large number of well-documented outbreaks1. A diagnosis of chronic fatigue syndrome (CFS) requires the exclusion of other known fatigue-related diseases and requires compliance with a clinical definition which is primarily characterized by unexplained, persistent or relapsing, chronic and debilitaticg fatigue lasting six or more consecutive months1, 2. The patient set derived by this process is heterogeneous in their polysymptomatic presentation and has proved very difficult to study clinically and scientifically. The question arises as to whether there exist any biochemical/physiological anomalies, which could be specifically associated with the CFS patients. This question can only be adequately addressed by a multidisciplinary approach, which integrates the utilization of biochemical, hematological, microbiological and clinical aspects of the disorder.
Analyses of the excretion of metabolites in the urine have indicated that CFS patients have a significantly altered pattern of excretion suggestive of an altered homeostasis3. Increases in an unusual marker, coded CFSUM1, Beta-alanine and tyrosine (a marker for non-fibrillar proteolysis), and decreases in serine, alanine and succinic acid were observed. Elevations in CFSUM1 and Beta-alanine were positively associated with increased symptom incidence and severity as well as musculo-skeletal symptoms and gastrointestinal symptoms. Conversely, reduced output of serine was associated with increasing severity of neurological dysfunction. These data provide evidence of a relationship between alterations in homeostasis and symptom expression.
Analyses of the CFS biochemical data by cluster analysis and multivariate techniques indicated that different types of CFS patients could be characterized on the basis of similarities in the metabolite profiles. The urine profiles can therefore be used to classify patients with similar excretion patterns to give relatively homogeneous sets of patients for investigation. Individual patients can be aligned with the metabolic profiles from our CFS research to assign their altered homeostasis to a particular CFS type.
In a similar manner, the plasma fatty acids profile can be used to differentiate CFS patients from control subjects. The CFS patients can be further characterized by clustering techniques to align patients with similar fatty acid homeostasis, again allowing homogenization of patient sets and classification of individual patients.
The capacity to group CFS patients into subsets using objectively derived measurements represents a major advance in CFS research, because it provides the capacity to develop treatment regimes based on objectively measured parameters, and minimizes the confounding effects of heterogeneity in future research programs.
1. Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: A working case definition. Ann Intern Med 1988; 108:387-389.
2. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med 1994; 121:953-959.McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis to chronic fatigue syndrome. Biochem Molecul Med 1996; 57: 73-80.
3. McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome. Biochem Molec Med 1996; 58:85-92.
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