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Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency

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JIMD Reports, Volume 36

Part of the book series: JIMD Reports ((JIMD,volume 36))

Abstract

Phenylalanine hydroxylase (PAH) deficiency is a genetic disorder characterized by deficiency of the PAH enzyme. Patients follow a phenylalanine-restricted diet low in intact protein, and must consume synthetic medical food (MF) to supply phenylalanine-free protein. We assessed relationships between dietary intake and nutrient source (food or MF) on bone mineral density (BMD) and bone turnover markers (BTM) in PAH deficiency. Blood from 44 fasted females 11–52 years of age was analyzed for plasma phenylalanine, serum BTM [CTx (resorption), P1NP (formation)], vitamin D, and parathyroid hormone (PTH). BTM ratios were calculated to assess resorption relative to formation (CTx/P1NP). Dual energy X-ray absorptiometry measured total BMD and age-matched Z-scores. Three-day food records were analyzed for total nutrient intake, nutrients by source (food, MF), and compliance with MF prescription. Spearman’s partial coefficients (adjusted for age, BMI, energy intake, blood phenylalanine) assessed correlations. All had normal BMD for age (Z-score >−2). Sixty-four percent had high resorption and normal formation indicating uncoupled bone turnover. CTx/P1NP was positively associated with food phenylalanine (r 2 = 0.39; p-value = 0.017), energy (r 2 = 0.41; p-value = 0.011) and zinc (r 2 = 0.41; p-value = 0.014). CTx/P1NP was negatively associated with MF fat (r 2 = −0.44; p-value = 0.008), MF compliance (r 2 = −0.34; p-value = 0.056), and positively with food sodium (r 2 = 0.43; p-value = 0.014). CTx/P1NP decreased significantly with age (p-value = 0.002) and higher PTH (p-value = 0.0002). Phenylalanine was not correlated with any bone indicator. Females with PAH deficiency had normal BMD but elevated BTM, particularly resorption. More favorable ratios were associated with nutrients from MF and compliance. Younger females had less favorable BTM ratios. Promoting micronutrient intake through compliance with MF may impact bone metabolism in patients with PAH deficiency.

Synopsis: Bone mineral density was normal in 44 females with PAH deficiency; however, bone turnover markers suggested uncoupling of bone resorption and formation, particularly in younger patients. Adequate nutrient intake from medical food and overall medical food compliance may positively impact bone turnover.

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Acknowledgments

We would like to thank the National PKU Alliance for support for DXA scans, Immunodiagnostic Systems (IDS) for support for bone turnover marker measurement, and the Atlanta Clinical and Translational Science Institute (ACTSI) for general study support including staff and facilities at Emory University Hospital’s Clinical Research Network and Children’s Hospital of Atlanta’s Pediatric Research Center.

Author information

Authors and Affiliations

  1. Nutrition and Health Sciences and Molecules to Mankind Programs, Laney Graduate School, Emory University, Atlanta, GA, USA

    Kathryn E. Coakley

  2. Division of Pediatric Endocrinology, Emory University School of Medicine, Atlanta, GA, USA

    Eric I. Felner

  3. Division of Endocrinology, Metabolism and Lipids, Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA

    Vin Tangpricha

  4. Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA

    Peter W. F. Wilson

  5. Metabolic Nutrition Program, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA

    Rani H. Singh

  6. Department of Individual, Family and Community Education, University of New Mexico, 604 Cagua Dr SE, Albuquerque, NM, 87108, USA

    Kathryn E. Coakley

Authors
  1. Kathryn E. Coakley
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  2. Eric I. Felner
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  3. Vin Tangpricha
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  4. Peter W. F. Wilson
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  5. Rani H. Singh
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Corresponding author

Correspondence to Kathryn E. Coakley .

Editor information

Editors and Affiliations

  1. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  2. Division of Metabolism and Children’s Research Centre, University Children’s Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  5. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Ertan Mayatepek, MD

Appendices

Author Contributions

Kathryn E. Coakley (KEC).

Eric I. Felner (EIF).

Vin Tangpricha (VT).

Peter W. Wilson (PWW).

Rani H. Singh (RHS).

KEC and RHS designed research; KEC, EIF, and RHS conducted research; KEC, VT, and PWW analyzed data; KEC wrote the paper; KEC and RHS had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding Author

Kathryn E. Coakley, PhD RD

Department of Individual, Family and Community Education

University of New Mexico

604 Cagua Dr. SE

Albuquerque, NM 87108

kcoakley@unm.edu

270-312-6086

Conflict of Interest Statement

No authors have competing interests related to this body of work.

Funding Details

The National PKU Alliance, Immunodiagnostic Systems, Maine Medical Center Research Institute, National Center for Advancing Translational Sciences of the National Institutes of Health under Award number UL1TR000454, and The Burroughs Wellcome Fund.

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Coakley, K.E., Felner, E.I., Tangpricha, V., Wilson, P.W.F., Singh, R.H. (2017). Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 36. JIMD Reports, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_39

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  • DOI: https://doi.org/10.1007/8904_2016_39

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