By Adem Lewis / in , , , , , , , , , , , /

Patricia Beggiato and her family run a restaurant in Washington, DC. About five years ago, their busy lives took a turn. “My husband always had allergies, heartburn and did not think that was anything to worry about. And then on July 10, 2010, he experienced what we thought was food poisoning after he ate shellfish and just never recovered.” During a vacation to Switzerland, he saw a doctor who suspected a mast cell disorder might be causing his symptoms. Mast cells, part of the body’s immune system, are packed with inflammatory chemicals that cause allergy symptoms when released. Mast cell activation disorders occur when the cells release too much of their contents. “The doctor there told us to find a doctor in the United States who could help us, and I thought, ‘Absolutely, no problem, I live in Washington, DC.’ But, upon returning, nobody would help us. My husband in the meantime could not eat, he couldn’t get out of bed, he had terrible pain, all over body rashes.” Eventually, they came to the National Institutes of Health, or NIH. Joshua Milner and Jonathan Lyons are physician-scientists at NIH’s National Institute of Allergy and Infectious Diseases. “My lab is very focused on finding answers about allergy by studying patients who have what look like genetic problems with allergy.” In the course of their work, the scientists had identified a different family with bad allergies and joint problems, including overly flexible joints. Multiple family members had these distinct symptoms, suggesting a genetic disorder. Interestingly, the scientists found that the affected family members all had a high blood level of tryptase, a marker associated with mast cell activation. It appeared that patients were inheriting tryptase elevations along with their symptoms. They have since identified other families with inherited mast cell activation disorders, including the Beggiatos, who participate in clinical studies at NIH. Patients may experience a range of symptoms, including anxiety; depression; irritable bowel syndrome, or IBS; chronic fatigue; feeling faint or dizzy; and chronic pain. Many, though not all, have high tryptase. Some patients experience symptoms from birth. Others, like Mr. Beggiato, develop them later in life, usually following a stressful event. Patricia Beggiato’s daughter Alessandra is one of several family members with high tryptase. “Basically, as long as I can remember, I’ve always had, you know, like random little things. I get allergies, get sick kind of easier, things of that nature. But nothing really major that sounded like it was anything different than normal.” Because the symptoms vary so widely in type and severity and can start at different points in life, mast cell activation disorders are difficult to recognize. “The frequency of mast cell activation disorders in general is likely largely underestimated in the general population. The frequency of high tryptase is really between three and seven percent.” “A lot of folks who have this are walking around and suffering and being told, ‘It’s all in your head.’ So here’s a real opportunity for us to show that, sometimes, when that happens, we can really find a genetic explanation for what it is that’s going on.” So far, there are no specific therapies for mast cell activation disorders, although treatments can help
manage some of the symptoms. The NIH team is continuing to gain expertise by studying affected families. “We now have what appears to be at least 40 families, with over 135 affected and unaffected family members.” The scientists are performing genetic analyses to pinpoint key differences between affected and unaffected family members. “By finding that, hopefully, that would be something that we could target. That change in their DNA may give us the answer to what to do about the problem, not just, ‘Oh, that’s why they have the problem.'” “Just having NIH there, especially with an open mind, to help us has been… it helps me sleep better at night.”

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