Why metabolism matters in Fanconi anemia

(Press-News.org) Experts at Cincinnati Children’s have uncovered striking metabolic differences in people with Fanconi anemia (FA), a rare genetic disorder that causes bone marrow failure and dramatically increases cancer risk.

The findings, published Nov. 28, 2025, in Science Advances, could reshape how clinicians think about nutrition and potentially cancer prevention in this vulnerable population. 

WHAT THE TEAM DISCOVERED 

In collaboration with the Bone Marrow Transplantation Program and the Fanconi Anemia Comprehensive Care Center at Cincinnati Children’s, researchers used a cutting-edge technique called “isotope tracing metabolomics.” Participants drank a small amount of glucose with specially “tagged” carbon atoms, allowing scientists to safely track how they moved through the body’s metabolic pathways and were 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, individuals with FA showed: 

Blood sugar that stayed high and a drop in the amount of energy their bodies burned after taking a glucose drink.  A shift toward burning fat for fuel, with higher levels of ketones—even though their bodies had plenty of glucose available.  Signs that their bodies weren’t responding well to insulin, including unusually high levels of certain amino acids.  “These patterns reveal a profound metabolic inflexibility,” says the study’s first and co-corresponding author Sara Vicente-Muñoz, PhD, a staff scientist in the Translational Metabolomics Facility within the Division of Pathology and Laboratory Medicine at Cincinnati Children’s. “Persons with FA appear to bypass normal glucose oxidation, which may influence both their overall health and cancer risk.” 

WHY THIS MATTERS 

Fanconi anemia affects nearly every organ system and predisposes patients to aggressive cancers. Understanding how FA rewires energy metabolism could lead to new strategies for improving health and reducing 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,” says Lindsey Romick, PhD, corresponding author and director of the Translational Metabolomics Facility. “Our next step is a feasibility study in children with FA to test whether a low-carbohydrate diet can improve metabolic health." 

Cincinnati Children’s is among a handful of institutions with experts like Vicente-Muñoz with deep expertise in stable isotope metabolomics. 

“Her rare skillset allows her not only to process and analyze exceptionally complex isotopic datasets, but also to interpret the resulting patterns in ways that reveal meaningful biological stories,” Romick says.  

While these results are an exciting step forward for individuals with FA, Romick and her collaborators from the Cancer & Blood Diseases Institute strongly caution families about making dietary changes on their own. “Persons with FA are medically fragile and need continued expert guidance,” notes Romick. “Families should consult with their child’s provider.” 

ABOUT THE STUDY 

Co-authors from Cincinnati Children’s 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, from the University of Kentucky also contributed to the study.

Research work for this study was supported by these core facilities at Cincinnati Children’s: the Research Flow Cytometry Facility, the Bionutrition Research Facility, and the Translational Metabolomics Facility. 

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). 

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