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Author Notes:

Kristen D Brantley, Email: kbrantley@g.harvard.edu.

KB: Developed study objective; completed data analysis, tables, graphs, and manuscript writing.

TD: Assisted with grant writing, study coordination, data collection, study documents, guidance to the primary author, review of data analysis methods and editing of manuscript drafts.

RS: Primary investigator with acquired funding; lead advisor on study design, analysis, patient recruitment and draft review.

All authors read and approved the final manuscript.

Special appreciation to the patients who participated in the study.

Thanks to Mary Jane Kennedy (project coordinator), Sarah Travis (research dietitian), additional faculty and staff within the Emory Genetics Clinic and Emory Genetics Laboratory who assisted with completion of the study.

Thanks also to Kathryn Coakley for her guidance and support.

Competing interests: Independent investigator sponsored trial with partial funding provided by BioMarin Pharmaceutical Inc.


Research Funding:

Partial funding through an independent investigator award from BioMarin Pharmaceutical Inc. Supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • Phenylketonuria
  • Tetrahydrobiopterin (BH4)
  • Sapropterin
  • B-vitamin deficiency
  • Iron deficiency
  • RISK
  • PKU

One-year follow-up of B vitamin and Iron status in patients with phenylketonuria provided tetrahydrobiopterin (BH4)


Journal Title:

Orphanet Journal of Rare Diseases


Volume 13, Number 1


, Pages 192-192

Type of Work:

Article | Final Publisher PDF


Background: People with Phenylketonuria (PKU) who respond to tetrahydrobiopterin (BH4) often decrease dependence on medical food (MF) following increased phenylalanine (phe) tolerance. Responders to BH4 may experience a reduction in certain nutrients if not compensated through intact foods or supplements. This study investigated B6, B12, folate, and iron status based on blood levels and dietary intake in patients with PKU responsive to BH4 over 1 year. Methods: Fifty-eight patients with PKU, ages 4-50 years were recruited and initiated on BH4 therapy. Patients were monitored for BH4 response, and nutritional status was recorded at regular intervals over 12 months. The analysis included 33 patients with known BH4 response status and complete nutritional data. Nutrient intake was determined by National Data System for Research (NDSR) analysis of self reported 3 day diet records and compared to Dietary Reference Intakes (DRIs). Blood biomarkers were analyzed by Quest Diagnostics and compared to laboratory reference ranges. Patient laboratory values were compared to controls from the National Health and Examination Survey (NHANES). Differences in nutrient intakes across time points were examined, stratified by age, using nonparametric methods. Statistical analyses were completed with SAS 9.4, with significance set at α = 0.05. Results: Medical food intake declined among pediatric (p < 0.01) and adult (p = 0.06) BH4 responders over 1 year. Among those < 18 years of age, mean percent of calories obtained from MF declined from 21.3 to 4.7%. In adults, percent calories from MF dropped from 19.5 to 4.0%. Though maintaining laboratory and dietary values within reference ranges, responders < 18 years experienced a significant decline in serum B12 (p = 0.01), dietary folate (p = 0.006), and dietary iron (p = 0.004) over the study. Conclusion: Although mean dietary and laboratory values for B12, B6, folate, and iron in BH4 responders and non-responders were adequate at baseline and 12-month follow-up, responders experienced a significant decline in serum B12 over 1 year, which may be explained by decreased intake of fortified MF. Both response groups had lower serum B12 than NHANES controls at baseline and 12 months. Results indicate a need to monitor B12 concentrations and consider micronutrient supplementation, with special attention to pediatric patients with PKU.

Copyright information:

© 2018 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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