Prevalence and Basic Defect of Orthostatic Intolerance

Research project P 14705 Prevalence and Basic Defect of Orthosthatic Intolerance Hugo RÜDIGER 09.10.2000 Orthostatic Intolerance (OI) is a syndrome characterised by adrenergic symptoms which occur when the subject rises from a supine position but it is not associated with orthostatic hypotension. Typical symptoms are headaches, lack of concentration, tremor, palpitations (heart rate increase by at least 30 beats per minute) , fatigue and syncopes. These symptoms are associated with high plasma norepinephrine levels. Although the clinical phenomenon is well established, the incidence is as yet unknown, above all because of the lack of detailed and clearly defined criteria and diagnostic guidelines. The pathophysiological mechanism of orthostatic intolerance is not yet identified as well. Numerous trials and studies have, however, shown that patients respond to a change in position from lying to standing by an exessive release of norepinephrine. An association between orthostatic intolerance and a norepinephrine transporter defect due to a chromosome 16q mutation has recently been established by gene sequencing (Shannon et al., N.Engl.J.Med., Feb.24, 2000), but the relevance of this defect in quantitative and qualitative terms is an open question. In Addition several case studies focused on possible connections between patients with 01 and those with Chronic Fatigue Syndrome (CFS). In a study by Schondorf, 40% of CFS patients were shown to also suffer from OI, while De Lorenzo found a rate of 28%. Therefore CFS patients will be included in the study as well. Our project aims at : determining the incidence of orthostatic intolerance, determining the incidence of Ala457Pro mutation in OI patients exploring the presence of Ala457Pro mutation in patients with Chronic Fatigue Syndrome.

Although not a disease in actual fact but rather a predisposition factor for the occurrence of orthostatic symptoms under conditions of increased orthostatic stress, orthostatic intolerance (OI) is of great relevance for occupational medicine. OI implies not only a substantial impairment of well-being and work performance, it represents a major safety risk for particular professions. To establish the diagnosis of OI a tilt table examination is indispensable. This diagnostic expenditure, however, is not possible for screening purposes. Therefore the present study was carried out to investigate whether a specific questionnaire can be used as a screening method for OI. The results of the study indicate that our questionnaire can be used as a valid and reliable screening tool for OI. This new questionnaire offers effective facilities in the diagnostic management. The second aim was to determine the frequency of a specific mutation of the norepinephrine-transporter gene in patients with OI. The specific mutation was not detected in any of fourteen OI patients. Its routine determination will therefore not be helpful to establish the clinical diagnosis of OI.