Abstract
Background
Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study.
Methods
In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored.
Results
Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3–8% in the PANS cohort, 1.4–2.0-fold higher than in the age- and sex-matched U.S. population. More stringent ferritin level cut-offs than the comparison CDC dataset were used.
Conclusion
Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association.
Impact
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Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population.
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Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss.
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Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.
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Acknowledgements
We acknowledge Grace Goodwin, Kayla Brown, Gabbi Kamalani, and Dr. Mark Goreman for assistance with data collection. We also acknowledge all the clinicians and staff at the Stanford Immune Behavioral Health Clinic, and Lucile Packard Children’s Hospital for their excellent care of patients with PANS, which allows us to research this disease. J.F. received research funding from the PANDAS Physicians Network and the National Institute of Mental Health, Pediatrics and Developmental Neuroscience Branch. She has also received funding for CME activities through the Foundation for Children with Neuroimmune Disorders. These organizations did not partake in this study.
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J.F. conceptualized and designed the study, supervised research assistants, interpreted data, and provided intellectual review of the manuscript. M.J. provided expertise regarding ferritin, anemia and study design, and revised the manuscript. H.K. conceptualized using the CDC data as a comparison dataset and performed the initial data analysis. Both H.K. and E.S. collected data and prepared the first draft of the manuscript. A.C. contributed to further data acquisition, data analysis and interpretation, and manuscript writing. M.T., T.W., and B.F., FNP-c, provided expert advice on chart reviews/data collection, and revised the manuscript. All authors approved the final version of the manuscript.
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Chan, A., Karpel, H., Spartz, E. et al. Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome. Pediatr Res 89, 1477–1484 (2021). https://doi.org/10.1038/s41390-020-1103-3
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DOI: https://doi.org/10.1038/s41390-020-1103-3
