AHMF: 98 Conference: Dunstan

The Development of Laboratory Tests for Investigating Chronic Fatigue and Pain Disorders

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
Australia
* Neurobiology Research Unit
Centre for Oral Health Research
University of Sydney
Westmead Hospital
Westmead
NSW 2084
Australia

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 debilitating 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. There is an urgent demand for a range of specialised tests to be developed for these chronic pain and fatigue disorders, to complement the basic pathology and assist the clinicians in classifying the various types of chronic fatigue and chronic pain. Data from studies involving analyses of plasma lipids and urinary excretion of metabolites together with their associations with symptom presentation3-5 have been used to classify patients with similar metabolic profiles into subgroups. These subgroups comprise relatively homogeneous sets of patients for investigation. Individual patients can also be aligned with the metabolic profiles from our CFS research to assign their altered homeostasis patterns to a particular CFS type. In addition, the test data can provide insight into potential management strategies, as certain host responses can be delineated, and nutrient deficiencies identified. Three types of specialist tests are currently available.

Analyses of the metabolites in the urine can indicate whether the patient has a significantly altered pattern of excretion representing an altered homeostasis, and whether or not that patient can be assigned to a previously defined type of chronic fatigue disorder. The data provided can indicate whether fibrillar or non-fibrillar catabolism is active in the patient, and whether any anomalies identified in the excretion pattern provide objective evidence for gut, neurological, energy and urea cycle dysfunction. An indication of specific amino acid deficiencies can also be obtained.
Analyses of plasma lipid profiles can indicate anomalies in lipid homeostasis and enable the assignment of a patient to a previously defined type of chronic fatigue disorder. The test can detect deficiencies in essential fatty acid composition, detect dysregulation of essential fatty acid desaturation and elongation, identify potential problems in ?-oxidation, and provide evidence for the presence of host responses to infectious agents.
Analyses of faecal aerobic and anaerobic microorganisms in conjunction with faecal lipid analysis can provide extensive data on the functional integrity of the gastrointestinal tract. The data can indicate overgrowths of specific organisms such as Bacteroides and low numbers of critical organisms such as Eschericia coli, Lactobacillus and Bifidobacterium spp. These data can lead to developing strategies for reconstituting the bowel flora. The faecal lipid data can further indicate evidence for dysfunctional bowel flora and in addition, detect evidence for malabsorption and the functional activities of the anaerobic organisms in their interconversions of bile and sterol products.

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.
3. 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.
4. 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.
5. McGregor NR, Dunstan RH, Butt HL, Zerbes M, Roberts TK, Klineberg IJ (1997). A preliminary assessment of the association of SCL-90-R psychological inventory responses with changes in urinary metabolites in patients with chronic fatigue syndrome. J Chronic Fatigue Syndrome 3:17-37