Orthostatic intolerance Orthostatic intolerance (OI) is a disorder of the autonomic nervous system (a subcategory of dysautonomia) characterized by the onset of symptoms upon standing. Symptoms include fatigue, lightheadedness, headache, weakness, increased heart rate/heart palpitations, anxiety, and altered vision. Often, patients have high plasma<unk>  (NE) concentrations (at least 600 pg/ml) in relation to sympathetic outflow upon standing, suggesting OI is a hyperadrenergic condition. The discovery of identical twin sisters who both had OI suggested a genetic basis for the disorder. A missense mutation on the<unk>  gene (SLC6A2) was discovered in which an alanine residue was replaced with a proline residue (Ala457Pro) in a highly conserved region of the transporter. The patients’ defective<unk>  had only 2% of the activity of the wild-type version of the gene. The genetic defect in the<unk>  protein results in decreased<unk>  activity that could account for abnormally high NE plasma levels in OI. However, 40 other OI patients did not have the same missense mutation, indicating other factors contributed to the phenotype in the identical twins. This discovery of the linkage with<unk>  mutations that results in decreased<unk>  reuptake activity and orthostatic intolerance suggests faulty NE uptake mechanisms can contribute to cardiovascular disease.
Norepinephrine transporter
Glutamate transporter
Neurotransmitter transporter
Prolactin-releasing peptide receptor
Thiamine transporter 1
Sodium-chloride symporter
Vesicular monoamine transporter
Mechanosensitive channels