A single gene mutation causes some immune system cells to shut down at body temperature and sends others into overdrive in the cold, creating a mix of ailments that researchers say constitutes a new medical syndrome.
The discovery helps explain a mysterious set of symptoms that doctors didn’t realize were linked until a chance encounter between an allergist at the National Institutes of Health and a patient with a disfiguring rash running from head to toe. The study was published Wednesday in the New England Journal of Medicine.
The patient was also highly sensitive to cold, which he overlooked since it ran in his family. A genetic link to the potentially deadly condition known as cold urticaria had never before been shown, said Joshua Milner, chief of the allergic inflammation unit at the National Institutes of Allergy and Infectious Diseases. Tests on his family members and others with the condition uncovered a variety of ailments, including autoimmune disease and antibody deficiency.
“Every single person had the cold sensitivity, but the other symptoms were variable and overlooked,” Milner said in a telephone interview. “One person was literally getting gamma globulin,” infusions of a protein that is found in the blood and includes antibodies to fight infection, he said.
Discussions with investigators around the nation yielded two unrelated families with similar symptoms, including a wayward immune response against their own tissue and a dearth of the infection-fighting antibodies needed to stay healthy.
Further investigation on 27 family members allowed scientists to find the cause: deletions in a single gene known as PLCG2 that’s involved in switching immune system cells off and on.