Experts at Cincinnati Children’s have discovered striking metabolic differences in people with Fanconi anemia (FA), a rare genetic disorder that causes bone marrow failure and significantly increases the risk of cancer.
The results, published on November 28, 2025 in Scientific advancescould reshape the way clinicians think about nutrition and potentially cancer prevention in this vulnerable population.
What the team discovered
In collaboration with the Bone Marrow Transplant Program and Cincinnati Children’s Fanconi Anemia Comprehensive Care Center, researchers used a cutting-edge technique called “isotope tracing metabolomics.” Participants drank a small amount of glucose with specially “marked” carbon atoms, allowing scientists to safely track how it moved through the body’s metabolic pathways and was processed in real time. This approach provided a first-of-its-kind, dynamic assessment of nutrient metabolism in this population.
The results were unexpected. Instead of using glucose efficiently, people with FA showed:
- Blood sugar that remained high and a drop in the amount of energy burned by their body after taking a glucose drink.
- A shift to burning fat for fuel, with higher levels of ketones, even though their bodies had plenty of glucose.
- Signs that their body was not responding well to insulin, including unusually high levels of certain amino acids.
“These models reveal profound metabolic rigidity,” says study first author and co-correspondent Sara Vicente-Muñoz, PhD, a scientist in the Translational Metabolomics Facility in the Division of Pathology and Laboratory Medicine at Cincinnati Children’s Hospital. “People with FA appear to bypass normal glucose oxidation, which may influence both their general health and their cancer risk. »
Why it matters
Fanconi anemia affects almost all organ systems and predisposes patients to aggressive cancers. Understanding how FA rewires energy metabolism could lead to new strategies to improve health and reduce cancer.
This study also shows how isotope tracing metabolomics can advance translational research. The same approach could help researchers uncover metabolic problems in many conditions, including diabetes, cancer and other rare genetic disorders.
This work reflects years of effort and highlights the power of advanced metabolomics to illuminate disease mechanisms. Our next step is a feasibility study in children with FA to test whether a low-carbohydrate diet can improve metabolic health.
Lindsey Romick, PhD, corresponding author and director of the Translational Metabolomics Facility
Cincinnati Children’s is one of a handful of institutions with experts like Vicente-Muñoz with deep expertise in stable isotope metabolomics.
“His rare skills enable him not only to process and analyze exceptionally complex isotope data sets, but also to interpret the resulting patterns in ways that reveal meaningful biological stories,” says Romick.
While these findings are an exciting advance for people with FA, Romick and colleagues at the Cancer & Blood Diseases Institute strongly caution families against making changes to their diets on their own. “People with FA are medically fragile and need ongoing expert advice,” notes Romick. “Families should consult their child’s healthcare provider. »
About the study
Cincinnati Children’s co-authors included Stella Davies, MBBS, PhD, MRCP (bone marrow transplantation and immune deficiency), Thomas Galletta, MD (oncology), Khyati Mehta, PhD (clinical mass spectrometry and biomedical informatics), and Suzanne Summer, MS, RD (Schubert Research Clinic). Andrew Lane, PhD, of the University of Kentucky also contributed to the study.
Research for this study was supported by these core facilities at Cincinnati Children’s: the Flow Cytometry Research Center, the Bionutrition Research Center, and the Translational Metabolomics Center.
Funding sources include the Fanconi Cancer Foundation and the Clinical and Translational Science Award (CTSA) program, grant UL1TR001425. The CTSA program is led by the NIH’s National Center for Advancing Translational Sciences (NCATS).
