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Modeling correlates of low bone mineral density in patients with phenylalanine hydroxylase deficiency

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Phenylalanine hydroxylase (PAH) deficiency is an inherited metabolic disorder requiring life-long restriction of dietary protein and phenylalanine-free medical food. Low bone mineral density (BMD) is reported, but factors associated with BMD Z-score (standard deviations from normal) are unknown. We examined associations between clinical and dietary parameters and total BMD Z-score in PAH deficiency patients, and developed models to predict Z-score. Data collected from patients >4 years of age (n = 88; mean age = 18.8 y; 61 % female) included demographic, clinical, laboratory, and dietary intakes. Adjusted Spearman’s correlation coefficients were calculated between parameters and TBMD Z-score, measured by dual energy x-ray absorptiometry (DXA). Parameters approaching significance (p-value < 0.10) were candidate predictors for four linear regression models predicting TBMD Z-score. To validate, model-predicted Z-scores were compared to DXA Z-scores. Mean TBMD Z-score was −0.326; 18 (20.4 %) had Z-score < −1. Z-scores were positively correlated with dietary vitamin D, calcium, and medical food intake and compliance with prescription, and negatively with dietary carbohydrate, sugar, caffeine intake, glycemic load, and prescribed medical food (grams protein/day; p-value < 0.05). The best model included medical food compliance, medical food intake, caffeine intake, and bone-specific alkaline phosphatase (r-square = 0.364). This model predicted Z-score category [normal or low (<−1)] with sensitivity = 66.7 %, likelihood ratio = 14.7, and AUC = 0.83 compared to DXA Z-score. No subjects had low BMD for chronological age (Z-score ≤ −2). Compliance with medical food prescription was the strongest predictor of TBMD Z-score. One model, if validated in a separate sample of patients with more cases of low BMD, showed potential to estimate TBMD Z-score using routine clinical patient parameters.

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Authors and Affiliations

  1. Doctoral Program in Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA

    Kathryn E. Coakley, Michael Goodman, Usha Ramakrishnan & Rani H. Singh

  2. Post-Doctoral Fellow, Department of Neurology, Emory University, Atlanta, GA, USA

    Teresa D. Douglas

  3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Michael Goodman

  4. Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Usha Ramakrishnan

  5. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Steven F. Dobrowolski

  6. Department of Human Genetics and Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA

    Rani H. Singh

  7. 2165 North Decatur Road, Decatur, GA, 30033, USA

    Kathryn E. Coakley

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  1. Kathryn E. Coakley
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  2. Teresa D. Douglas
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Correspondence to Kathryn E. Coakley.

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Conflict of interest

Rani H Singh has participated in and/or received research funding for clinical trials related to PAH deficiency. Rani H Singh confirms independence from the sponsors; the content of the article has not been influenced by the sponsors.

Kathryn E Coakley, Teresa D Douglas, Usha Ramakrishnan and Michael Goodman declare that they have no conflict of interest.

Informed consent

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (Emory Institutional Review Board and national) and with the Helsinki Declaration of 1975, as revised in 2000.

Informed consent was obtained from all patients for being included in the study.

Animal rights

This article does not contain any studies with animal subjects performed by any of the authors.

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Communicated by: Nenad Blau

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Coakley, K.E., Douglas, T.D., Goodman, M. et al. Modeling correlates of low bone mineral density in patients with phenylalanine hydroxylase deficiency. J Inherit Metab Dis 39, 363–372 (2016). https://doi.org/10.1007/s10545-015-9910-0

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  • DOI: https://doi.org/10.1007/s10545-015-9910-0

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