Scientists at the National Institutes of Health have identified a genetic explanation for a syndrome characterized by multiple frustrating and difficult-to-treat symptoms, including dizziness and lightheadedness, skin flushing and itching, gastrointestinal complaints, chronic pain, and bone and joint problems. Some people who experience these diverse symptoms have elevated levels of tryptase — a protein in the blood often associated with allergic reactions. Multiple copies of the alpha tryptase gene drive these tryptase elevations and may contribute to the symptoms, according to a new study led by investigators at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
Other studies have indicated that four to six percent of the general public has high tryptase levels. While not all of these people experience symptoms, many do, raising the possibility that this mildly prevalent trait in some cases drives the symptoms, although how it does so remains unclear….
Previously, NIAID researchers had observed that a combination of chronic and sometimes debilitating symptoms, such as hives, irritable bowel syndrome and overly flexible joints, runs in some families and is associated with high tryptase levels. Many affected family members with high tryptase also reported symptoms consistent with disorders of autonomic nervous system function (dysautonomia), including postural orthostatic tachycardia syndrome (POTS), which is characterized by dizziness, faintness and an elevated heartbeat when standing up.
“Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number”, Jonathan J Lyons et al.
Corresponding author: Joshua D Milner
Nature Genetics (2016), doi:10.1038/ng.3696