BACKGROUND: Orthostatic intolerance (OI) is a syndrome characterized by 
lightheadedness, palpitations, fatigue, blurred vision, dizziness, chest 
discomfort, cognitive impairment, and occasionally syncope. These symptoms 
usually occur after upright posture and are associated with tachycardia and high 
plasma concentrations of norepinephrine. It has been proposed that a mutation in 
exon 9 of the norepinephrine transporter gene (Ala457Pro), resulting in more 
than 98% loss of function compared with the wild type, might provide a 
pathogenetic mechanism to explain the clinical symptoms of patients with OI.
METHODS: We studied 46 young men from military service who had sought medical 
advice because of dizziness while standing. Every patient underwent a tilt-table 
test, with monitoring of blood pressure, heart rate, and plasma catecholamines 
in supine position and during 30 minutes of standing. Fourteen patients showing 
the full-blown OI syndrome (30 bpm increase in heart rate and 600 pg/mL plasma 
norepinephrine levels while standing) underwent direct DNA sequencing of exon 9 
of the norepinephrine-transporter gene.
RESULTS AND CONCLUSIONS: The specific mutation (Ala457Pro) was not detected in 
any of the 14 OI patients. Based on these findings, we doubt that this specific 
genetic transport defect is a frequent cause of the impaired uptake of 
norepinephrine in OI patients. Its routine determination will therefore not be 
helpful to establish the clinical diagnosis of OI.