Abstract
Classic galactosemia (CG) is an autosomal recessive disorder of galactose metabolism that affects approximately 1/50,000 live births in the USA. Following exposure to milk, which contains large quantities of galactose, affected infants may become seriously ill. Early identification by newborn screening with immediate dietary galactose restriction minimizes or prevents the potentially lethal acute symptoms of CG. However, more than half of individuals with CG still experience long-term complications including cognitive disability, behavioral problems, and speech impairment. Anecdotal reports have also suggested frequent gastrointestinal (GI) problems, but this outcome has not been systematically addressed. In this study we explored the prevalence of GI symptoms among 183 children and adults with CG (cases) and 190 controls. Cases reported 4.5 times more frequent constipation (95% CI 1.8–11.5) and 4.2 times more frequent nausea (95% CI 1.2–15.5) than controls. Cases with genotypes predicting residual GALT activity reported less frequent constipation than cases without predicted GALT activity but this difference was not statistically significant. Because the rigor of dietary galactose restriction varies among individuals with galactosemia, we further tested whether GI symptoms associated with diet in infancy. Though constipation was almost four times as common among cases reporting a more restrictive diet in infancy, this difference was not statistically significant. These data confirm that certain GI symptoms are more common in classic galactosemia compared to controls and suggest that future studies should investigate associations with residual GALT activity and dietary galactose restriction in early life.
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Acknowledgments
First, we thank the Galactosemia Foundation and the many individuals and families who participated in this study; without them none of this work would have been possible. We are also grateful to Drs. Tanvi Dhere and Sandy van Calcar for invaluable guidance in the early stages of this project, and to Dr. K. Alaine Broadaway for early assistance with R. This study was funded in part by NIH grant R01 DK059904 (to JLFK). KAS was supported at different times by funds from training grant ID#1008188 (BWF), training grant T32GM008490 (NIH), and NRSA F31DK107229 (NIH).
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Communicated by: Ivo Barić, M.D., PhD, Professor of Pediatrics
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None of the authors have any competing interests to declare.
Human Subjects Ethics Approval
This study was conducted with approval of the Emory University Institutional Review Board (Emory IRB Protocol # 00024933, PI: JL Fridovich-Keil) and all study volunteers completed appropriate informed consent prior to participation.
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Kelly A. Shaw declares that she has no conflict of interest.
Jennifer G. Mulle declares that she has no conflict of interest.
Michael P. Epstein declares that he has no conflict of interest.
Judith L. Fridovich-Keil declares that she has no conflict of interest.
Author Contributions
Kelly A. Shaw helped to design the study, collected much of the data, conducted most of the statistical analyses, wrote the original draft of the manuscript, and contributed to editing the final manuscript.
Jennifer G. Mulle contributed to the study design, statistical analyses, and manuscript editing.
Michael P. Epstein contributed to the study design, statistical analyses, and manuscript editing.
Judith L. Fridovich-Keil oversaw the project and contributed to the study design and preparation and editing of the final manuscript.
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Shaw, K.A., Mulle, J.G., Epstein, M.P., Fridovich-Keil, J.L. (2016). Gastrointestinal Health in Classic Galactosemia. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 33. JIMD Reports, vol 33. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_575
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DOI: https://doi.org/10.1007/8904_2016_575
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