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

  • Kathryn E. CoakleyEmail author
  • Eric I. Felner
  • Vin Tangpricha
  • Peter W. F. Wilson
  • Rani H. Singh
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)


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 (r2 = 0.39; p-value = 0.017), energy (r2 = 0.41; p-value = 0.011) and zinc (r2 = 0.41; p-value = 0.014). CTx/P1NP was negatively associated with MF fat (r2 = −0.44; p-value = 0.008), MF compliance (r2 = −0.34; p-value = 0.056), and positively with food sodium (r2 = 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.


Bone metabolism Bone mineral density Bone turnover markers Dietary intake Medical food Phenylalanine hydroxylase deficiency 



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.


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Kathryn E. Coakley
    • 1
    • 6
    Email author
  • Eric I. Felner
    • 2
  • Vin Tangpricha
    • 3
  • Peter W. F. Wilson
    • 4
  • Rani H. Singh
    • 5
  1. 1.Nutrition and Health Sciences and Molecules to Mankind Programs, Laney Graduate SchoolEmory UniversityAtlantaUSA
  2. 2.Division of Pediatric EndocrinologyEmory University School of MedicineAtlantaUSA
  3. 3.Division of Endocrinology, Metabolism and Lipids, Atlanta VA Medical CenterEmory University School of MedicineAtlantaUSA
  4. 4.Clinical Cardiovascular Research InstituteEmory University School of MedicineAtlantaUSA
  5. 5.Metabolic Nutrition Program, Department of Human GeneticsEmory University School of MedicineAtlantaUSA
  6. 6.Department of Individual, Family and Community EducationUniversity of New MexicoAlbuquerqueUSA

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