Children’s Hospital of Philadelphia, Clinic for Special Children discover ultra rare form of neuroinflammatory disease is much more common in Old Order Amish than general population
By working closely with the Amish community, clinicians are able to gather the critical information to effectively treat patients with a genetic neuroinflammatory condition
Philadelphia and Gordonville, PA, August 12, 2025 – Researchers from Children’s Hospital of Philadelphia (CHOP) and the Clinic for Special Children found that complement factor I (CFI) deficiency, an ultra-rare genetic disorder that can cause debilitating neuroinflammation, is more than 4500 times more likely to be found in individuals of Old Order Amish ancestry than the rest of the global population. These findings could help clinicians better recognize the disease and develop a standard-of-care, particularly for Amish patients affected by this disease. The findings were published today by the Journal of Allergy and Clinical Immunology.
CFI deficiency is a genetic disorder that affects the immune system, often resulting in a high likelihood of recurrent bacterial infections, and in some cases, vascular and neuroinflammatory symptoms requiring hospitalization and acute management. In addition to genetic factors, ethnic background or epigenetic influences like lifestyle, environmental exposures and diet can influence the trajectory of the disease, which is estimated worldwide to affect fewer than one in a million births but as high as 1 in 730 members of the Old Order Amish community.
The Clinic for Special Children, which provides clinical care to children and adults with complex medical disorders and has a specific focus on the treatment and research of disorders affecting the Old Order Amish and Mennonite communities, was alerted to an Old Order Amish patient at CHOP presenting with acute neuroinflammatory symptoms of unknown cause. Rapid exome sequencing identified a variant of unknown significance in the gene CFI, which was found to be the underlying cause of her disease and directed her targeted management and recovery. This case motivated researchers to determine if other members of the Old Order Amish community also harbored this genetic finding, as they share a common genetic heritage, agrarian lifestyle, and environmental exposures. Further investigtion found it was quite common and contributed to disease in the multiple Amish individuals.
“The first patient presented with headache, decreased consciousness, and weakness on one side of her body, which an MRI confirmed was due to brain inflammation. She was transferred to CHOP due to the severity of her condition and ultimately needed neurosurgical intervention,” said co-senior study author Vincent J. Carson, MD, a pediatric neurologist with the Clinic for Special Children. “Rapid exome sequencing, which can provide genetic diagnoses in a matter of days, was done at CHOP and confirmed the diagnosis of CFI deficiency. As a result, she was treated with a specific monoclonal antibody that blocks the complement cascade, called Eculizumab. This resulted in the resolution of the brain inflammation, leading to a full recovery.”
The Clinic for Special Children knew that patients with Old Order Amish ancestry carried the CFI gene, but did not yet know that a particular variant caused disease. This led to a collaboration between the Clinic for Special Children and CHOP to learn more about the incidence of brain inflammation in CFI deficiency.
“What started as a case report turned into a population study,” said co-senior study author Neil D. Romberg, MD, an attending physician with the Division of Allergy and Immunology at CHOP. “There is a striking level of enrichment of this genetic variant in the Amish community, and now that our understanding of this disease in this population has been expanded, we can offer personalized treatment plans for these patients to help them recover and get back to a normal life within their community.”
“There are about 430 genetic disorders that we treat and counting, and since hundreds of thousands of Amish and Mennonites living in this country can trace their ancestry back to about 80 Amish founders and 240 Mennonite effective founders, we know that certain disorders are much more prevalent while others that are more common in the general population rarely affect this community,” said Laura Poskitt, DO, medical director of the Clinic for Special Children. “With the consent of our patient communities, we’ve been able to maintain a database that helps us learn more about genetic variants that may be more common in these patients in particular.”
When focusing on 11 Amish patients who had this variant, five of the patients had presented with critical neuroinflammatory diagnoses. Those patients recovered with the aid of high dose steroids, and one patient had a clinical response to eculizumab, a monoclonal antibody used to treat several diseases linked to the immune system.
“We have heard from patients treated for this disease that they’ve been able to recover and get back to being active members of their community, so we want to make sure we can properly identify any potentially affected patient and provide them with effective options for managing this disorder,” said first study author Whitney Reid, MD, an attending physician in the Division of Allergy and Immunology at CHOP. “In speaking with this community, they are asking good questions and want to be involved in ways that can not only help affected Amish but anyone who is impacted by this disease.”
“Getting to the root cause of the disease is a game changer,” Carson said. “All patients with inflammation of the brain or spinal cord who have Amish heritage should be tested for CFI deficiency. Knowing this allows us to use targeted treatments, such as eculizumab, and change the course of the disease.”
This study was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases grants AI146026, AI184976 and AI179680, the Jeffrey Modell Foundation , the Gail B. Slap Department of Pediatrics Fellowship Award, the Ruth L. Kirschstein T32 National Research Service Award, the Dr. Steven Douglas Memorial Fund and the Sayer family.
Reid et al, “Complement Factor I Deficiency-Associated Neuroinflammatory Disease Among Old Order Amish.” J Allergy Clin Immunol. Online June 29, 2025. DOI: 10.1016/j.jaci.2025.06.021.
About Children’s Hospital of Philadelphia:
A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.
About the Clinic for Special Children: The Clinic for Special Children is a non-profit organization located in Lancaster County, PA, that provides primary care and advanced laboratory services to children and adults who live with genetic or other complex medical disorders. Founded in 1989, the organization provides services to over 1,700 individuals and is recognized as a world leader in translational and precision medicine. The organization is primarily supported through community fundraising events and donations. For more information, please visit www.ClinicforSpecialChildren.org.
Journal
Journal of Allergy and Clinical Immunology
Method of Research
Case study
Subject of Research
People
Article Title
Complement Factor I Deficiency-Associated Neuroinflammatory Disease Among Old Order Amish
Laser therapy enhances treatment of fungus resistant to conventional medication
Researchers have managed to reduce Candida albicans’ resistance to fungicides by incorporating photodynamic inactivation techniques into the treatment. Technology can be used in both human healthcare and the prevention of food contamination.
Fundação de Amparo à Pesquisa do Estado de São Paulo
image:
The hyphae of C. albicans form a biofilm that is almost impenetrable to drugs. Photodynamic inactivation (PDI) therapy managed to “break” these barriers
view moreCredit: Gabriela G. Guimarães et al
Researchers at the Optics and Photonics Research Center (CePOF) have succeeded in increasing the susceptibility of the fungus Candida albicans to drug treatment through light-activated therapy. The results of the study offer a promising alternative in the fight against antimicrobial resistance, a growing global problem that occurs when bacteria, viruses, fungi, and other parasites develop genetic mutations that render them resistant to drugs.
In the study, published in the journal Photochemistry and Photobiology, the researchers evaluated photodynamic inactivation (PDI) combined with the antifungal amphotericin B (AmB) to control the growth of the fungus, particularly its yeast (single-celled) and hyphae (filamentous colony) forms.
The results showed that combining the two treatments reduced the C. albicans growth by 75% in the yeast form and by 87.5% in the hyphae form. In addition, two sessions of PDI further increased antifungal efficacy, particularly against hyphae, which were more sensitive to the treatment.
“It’s a technique that consists of using a molecule [in this case curcumin] and activating it with blue light. Activation, in the presence of oxygen, causes the molecule to produce free radicals, thereby inducing oxidative stress, killing or weakening the pathogen,” explains Vanderlei Bagnato, coordinator of CePOF, a FAPESP Research, Innovation, and Dissemination Center (RIDC) based at the São Carlos Institute of Physics of the University of São Paulo (IFSC-USP) in Brazil. “In the case of C. albicans, mainly in the hyphae, which form a biofilm that’s almost impenetrable to drugs, photodynamic therapy was able to ‘break’ these colonies, resulting in the potentiation of the antifungal effect.”
The study involved photodynamic inactivation using 2.5 μM (micrometers) curcumin, which was activated by 450 nm (nanometers) LED light and different concentrations of the antifungal AmB.
An imminent danger
C. albicans is naturally present in the human body and is usually harmless. However, it can cause skin manifestations such as thrush or vaginal candidiasis. In more serious cases, the fungus can cause systemic candidiasis, an invasive blood infection. This serious condition is being diagnosed more frequently in intensive care units (ICUs) due to the growing number of immunocompromised patients and increased microbial resistance.
“There’s growing resistance to fungi, and C. albicans is no exception. It’s a very common fungus, but there are already cases of patients who have died from resistant systemic infections. Therefore, it’s very important to anticipate the problem and present an alternative that allows for more effective combat against the fungus without side effects or the need for excessive medication use,” says Gabriela Gomes Guimarães, a researcher at CePOF and first author of the study.
Guimarães explains that the decision to begin photodynamic inactivation tests on fungi using C. albicans was motivated by the two morphologies of the species. “The fungus forms both yeasts and hyphae, which form biofilms. Therefore, the fact that it worked so well for C. albicans gives us confidence to conduct new tests on other species, such as C. auris, an emerging fungus that’s causing concern, has shown resistance to treatment, and can be fatal,” says the researcher.
Applications in food
In addition to testing the effects of photodynamic therapy on other fungal species that pose a threat to human health, the researchers will conduct studies focused on food safety. “The proof of principle we’ve just published on C. albicans allows us to conduct studies on the application of photodynamic therapy in food decontamination. Fungi are also a problem in grain contamination, for example. Therefore, our next step is to test the application of this technique in storage silos, for example,” Bagnato anticipates.
CePOF has been conducting various laser research projects aimed at advancing treatments for bacteria, viruses, and other diseases, including cancer and fibromyalgia (read more at: agencia.fapesp.br/50500).
“The principle is always the same: activate a molecule with a laser so that it oxidizes. What varies in each case is the application, the amount of light, color temperature, amount of drug, and how much of the pathogen is eliminated or inactivated,” Bagnato summarizes.
Jennifer Soares, a member of CePOF and a FAPESP scholarship recipient, explains that the researchers are also concerned with using molecules that are compatible with human health and the environment.
“Curcumin, for example, is a compound found in curry and has already been approved for use in humans. But there’s also concern about how to apply the light. Our studies have shown that blue light, due to its wavelength, is ideal for treating superficial infections such as in the throat. That’s why we’re developing devices capable of illuminating the tonsils, for example. Red or infrared light, on the other hand, is more suitable for treating deep infections, such as pneumonia, which requires devices adapted to illuminate the chest area,” she explains.
CePOF also conducts studies focused on treating cervical cancer by applying medication and photosensitizing molecules through specific routes, such as the intravaginal canal.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
Journal
Photochemistry and Photobiology
Article Title
Overcoming resistance of Candida albicans using photodynamic inactivation
Fast, accurate, low-cost diagnostics: No lab required
Ultra-sensitive test could transform global health care
Arizona State University
image:
At the core of a new diagnostic test created by ASU researchers are tiny gold nanoparticles, engineered to detect extremely small amounts of disease-related proteins. The device is so sensitive that it can detect disease from just a few hundred molecules in an extremely small fluid sample — a fraction of a single drop. This sensitivity is nearly 100,000 times greater than that of standard laboratory tests.
view more
Credit: Graphic by Jason Drees
Researchers at Arizona State University have developed a breakthrough diagnostic tool that could transform how quickly and reliably we detect illnesses like COVID-19, Ebola, AIDS or Lyme disease. The test uses just a single drop of blood, costs a couple of dollars and delivers results in only 15 minutes.
In a new study, the researchers show the test can detect the virus that causes COVID-19 with pinpoint accuracy, clearly distinguishing it from other infections.
The new diagnostic device, called NasRED (Nanoparticle-Supported Rapid Electronic Detection), is simple and portable enough to be used almost anywhere — from remote rural clinics to busy urban hospitals. The tool provides lab-quality accuracy without expensive equipment and does not require specialized training, giving it the potential to become a public health game changer.
“We have the speed and ease of use of a rapid antigen test with sensitivity that’s even better than lab-based tests,” says Chao Wang, lead author of the new study. “This is very difficult to achieve.”
Wang is an associate professor with the Biodesign Center for Molecular Design and Biomimetics and ASU’s School of Electrical, Computer and Energy Engineering. He is joined by ASU researchers Yeji Choi, Seyedsina Mirjalili, Ashif Ikbal, Sean McClure, Maziyar Kalateh Mohammadi, Scott Clemens, Jose Solano, John Heggland, Tingting Zhang and Jiawei Zuo.
The research appears in the current issue of the journal ACS Nano.
Halting the spread of infectious diseases
Infectious diseases are one of humanity's deadliest threats, causing immense suffering and economic damage worldwide. Collectively, infectious diseases cause over 10 million deaths around the world each year, and they are the leading cause of death in low-income countries.
Nearly 800,000 Americans die or are permanently disabled every year due to diagnostic errors, according to a study published in BMJ Quality & Safety. Many of these cases involve infections or vascular events that might have been treatable if caught early.
In many low- and middle-income countries, access to reliable diagnostic testing is limited or nonexistent. Expensive equipment, shortages of trained personnel and long turnaround times all contribute to delayed or missed diagnoses — often with deadly consequences.
A fast, affordable and portable test like NasRED would enable frontline health workers globally to detect infections early and respond before outbreaks spiral out of control.
“In many parts of the world, including the U.S., diseases are spreading, but people often don’t get tested — even for something like HIV. Ideally, you’d want to test them regularly, to catch infections early,” Wang says. “For example, people who use injection drugs are at higher risk for HIV or HCV, but they may be living in the streets and hard to reach. If we don’t test them consistently over time, we may miss the chance to intervene — until they develop serious complications like cancer or liver disease, when it’s much harder to treat.”
Striking diagnostic gold
At the core of the new test are tiny gold nanoparticles, engineered to detect extremely small amounts of disease-related proteins. Researchers coat these nanoparticles with special molecules designed to detect specific diseases.
Some nanoparticles carry antibodies, tiny molecules that act like magnets. Antibodies stick to proteins released by viruses or bacteria when they infect the body. Other nanoparticles carry antigens, fragments of proteins taken directly from viruses or bacteria themselves. These naturally attract antibodies produced by the body to fight infections.
Once coated, these nanoparticles are combined with a tiny sample of bodily fluid, such as a drop of blood, saliva or nasal fluid. If a disease is present, most nanoparticles will sink to the bottom of the tube. If there is no disease, they will remain suspended throughout the liquid.
The NasRED device shines a small beam of LED light through the liquid at the top of the tube. The team built a custom electronic detector that senses how much light gets through the tube. More light means the nanoparticles have sunk to the bottom, leaving the top fluid clearer, meaning that the disease is present.
Accurate, accessible and affordable
The device is so sensitive it can detect disease even when only a few hundred molecules are present in a tiny fluid sample — just a fraction of a single drop. This is a concentration nearly 100,000 times lower than what standard laboratory tests require.
Adding to its promise is NasRED’s portability and affordability. The current gold standards for testing, like PCR or ELISA, require expensive equipment and trained technicians. NasRED is compact and user-friendly. The researchers estimate each test costs $2, making it ideal for use in low-resource or remote locations.
NasRED has the potential to fill a critical diagnostic gap, especially for diseases that are difficult to detect early, such as hepatitis C, HIV or Lyme disease. It is also promising for emerging outbreaks with low prevalence but high risk. Such diseases often go undiagnosed because running a lab test for just one or two patients isn’t cost effective. NasRED bridges that gap by offering a highly sensitive test that works immediately and economically at the point of care.
While NasRED currently requires small, benchtop machines for spinning and mixing samples, the researchers are working to further miniaturize and automate the process. With continued development, the technology might one day become a convenient home test, similar to existing rapid COVID-19 tests. However, it would have vastly superior sensitivity and broader applications.
Significant leap forward in diagnostics
NasRED dramatically surpasses existing diagnostic standards. The new study shows that NasRED is roughly 3,000 times more sensitive than ELISA, requires 16 times less sample volume, and delivers results approximately 30 times faster.
An earlier version of the technology detected Ebola in a tiny sample of blood. “For the new technology, we pushed the sensitivity down to the attomolar range,” Wang says. That’s like detecting a single drop of ink in 20 Olympic swimming pools.
The technology holds promise for detecting viral loads directly from bodily fluids without the complicated sample preparation used in PCR-based methods. In preliminary tests with actual coronavirus particles, NasRED achieved sensitivities comparable to Abbott ID NOW, a popular molecular test for many diseases such as COVID-19.
“One of the strengths of our sensor is that it’s highly modular,” Wang says. "The nanoparticles are designed so that we can easily swap in different proteins, allowing the same platform to be adapted for many different diseases. We’ve already demonstrated this approach in our research on Shiga toxin-producing E. coli, as well as cancer biomarkers, Alzheimer’s-related proteins, Lyme disease and African swine fever.”
Wang recently received the Bay Area Lyme Foundation Emerging Leader Award and will make use of the high sensitivity and portability of this new technology to detect early Lyme infection.
As the technology evolves, its range of applications may extend beyond infectious diseases. Early detection of cancers, real-time monitoring of chronic illnesses and improved surveillance of public health threats are all within reach.
Revolutionizing disease diagnosis [VIDEO]
Journal
ACS Nano
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
Nanoparticle-Supported, Rapid, and Electronic Detection of SARS-CoV-2 Antibodies and Antigens at the Subfemtomolar Level
Article Publication Date
11-Aug-2025
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