[Mast cells from a sinus stained in blue. Image via Wikimedia Commons & CC 2.0]
On July 10, 2010, a DC restauranteur came down with what seemed to be food poisoning. He had no energy and no appetite. Rashes flared up. He could barely get out of bed. First hours and then days dragged by without any relief from the symptoms.
The restauranteur’s family sought out doctor after doctor, until finally they were referred to a lab at the NIH (National Institutes of Health) that studies how allergies pass down through families.
His symptoms fit a diagnosis of Mast Cell Activation Syndrome, (MCAS) a disorder where a type of immune cells called mast cells release chemicals that send other immune cells into a destructive frenzy. Ideally, mast cells detect infection and spur other immune cells into action. However, some people’s mast cells have a hair trigger. When mast cells release their chemical contents too often, immune cells end up attacking healthy tissue, causing allergies, stomach issues, and heart palpitations.
[Above: An NIH-produced video about MCAS and Milner’s research into mast cell activation genetics.]
Unfortunately, most treatments for MCAS aim at the symptoms, not the root cause. But the NIH team delved deeper into the genetics and found a pattern: many MCAS-related symptoms run in families.
And oddly enough, hyperflexible joints, dysautonomia, and baby teeth that fail to fall out also ran in many of those families. [Correction 6/15: A commenter has pointed out that “hyperflexible” and “hypermobile” are not interchangeable terms. The term “hypermobile” refers to joints that can move outside the typical range of motion due to laxness in ligaments. “Hypermobility” is also sometimes called “double-jointedness.”] Many of these symptoms skipped generations, only showing up occasionally in individuals, but genetic sequencing revealed the correlation wasn’t coincidence.
In October, NIH scientist Joshua Milner and his team described the genetic disorder in a paper in Nature Genetics. According to the team’s paper, 4-6% of the U.S. population has the genes that predispose them to this syndrome–which has been tentatively named alpha-tryptasemia or “alpha-T”.
The symptoms can be cryptic and unrelenting: Dizziness, chronic pain, irritable bowels, and fainting. For many patients with these conditions, there’s no explanation and no treatment. “These [symptoms] are really all triggers to get an eyeroll from a doctor,” said Milner. But for a sizeable portion of population, these seemingly unrelated problems might be part of the previously undiscovered genetic disorder.