Researchers Identify Ultra-Rare Genetic Disorder in Amish Communities
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Asia Tabb
AIRED; September 9, 2025
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A collaborative study by the Clinic for Special Children in Lancaster and the Children’s Hospital of Philadelphia has identified an ultra-rare genetic disorder called complement factor I (CFI) deficiency, which is significantly more prevalent in individuals of Old Order Amish ancestry.
“CFI deficiency… is a protein in our bodies that is a really critical component of our immune system called the complement system,” explained Dr. Laura Poskitt, Medical Director of the Clinic for Special Children. “The complement system plays a really important role in our early immune response… When you don’t have CFI, you can get over-activation and inflammation in the immune system. This can cause brain injury, spinal cord inflammation, and can be really disabling.”
While CFI deficiency is extremely rare in the general population, researchers found it to be more than 4,500 times more likely to occur in people of Old Order Amish ancestry. Dr. Poskitt attributed this to a genetic phenomenon known as the “founder effect.” “Out of the about 400,000 Amish individuals living in the U.S., they descended from about 80 to 100 individuals who started that gene pool,” she said. “Because of that limited gene pool, some disorders, like CFI deficiency, are much more common.”
Dr. Poskitt stressed that this is not due to close familial marriages, as sometimes assumed, but rather the historical genetics of the community. She also compared it to other genetic conditions, noting, “Cystic fibrosis is common in people of Western European heritage, but virtually non-existent in the Amish. Other disorders, like CFI deficiency, are more common because of the small founder population.”
Early identification is key to preventing serious complications. Dr. Carson Pediatric Neurologist at the Clinic for Special Children explained, “Patients are at risk for infections because they use up all their complement proteins, and they’re also at risk for brain and spinal cord inflammation… Children or adults can get worse quickly, presenting with weakness, confusion, fatigue, or severe headache. When that happens, they need emergent care.” Preventative measures include vaccinations and prompt treatment with antibiotics when infections arise.
The research represents a successful collaboration between two institutions. “It was a very good example of how a big institution like Children’s Hospital of Philadelphia… can work together with a team like ours, which has a lot of experience with genetic disorders in the Amish and Mennonite communities,” said Dr. Poskitt. The partnership allowed clinicians to combine patient care with detailed molecular research to better understand how CFI deficiency manifests in the Amish population.
The findings could help clinicians worldwide better recognize and manage this disorder, particularly in communities where it occurs more frequently, and ultimately establish standards of care to protect patients from severe complications.