Bone mineral density in French adults with early-treated phenylketonuria

Phenylketonuria (PKU) treatment requires a low-phenylalanine (Phe) diet limiting natural protein intake, using medical low-protein foods and Phe-free amino acids (AA) supplements along with micronutriments' supplies. Current recommendations suggest maintaining this diet for life to prevent neuro-psychological effects of high Phe concentrations. The long-term consequences of such a diet are poorly understood, particularly on bone health. Our study aimed to assess the prevalence of low bone mineral density (BMD) (Z-score ≤ -2, for vertebral and/or femoral site) in adults with PKU and to investigate associated risk factors, in the French ECOPHEN cohort. The study included 171 patients with 67.3 % of women and a median age of 27 years old. The median femoral and vertebral Z-scores of BMD were both - 0.6. Only 11.4 % of patients had a low BMD. Compared to patients with normal BMD, patients with low BMD had a lower body mass index (BMI) (median 20.4 versus 24.4 kg/m<sup>2</sup>, p = 0.002), and were more likely to have never stopped their diet (58.8 % versus 31.8 %, p = 0.029). They also had higher total protein intake (1.1 versus 0.9 g/kg/day, p = 0.015), with more proteins from AA supplements (0.80 vs 0.53 g/kg/day, p = 0.010). In multivariate analysis, younger patients born after 1990 and who never stopped diet had a 4.7 times risk to have low BMD (p = 0.005), after adjustment on age, sex, BMI. In summary, our study identified a subgroup of PKU adult patients with low BMD and showed that prolonged low natural protein diet is associated with low BMD.

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Publication Details

Journal
Molecular Genetics and Metabolism
Published
2025-01-27
DOI
https://doi.org/10.1016/j.ymgme.2025.109044
Citations
2
Primary Topic
Metabolism and Genetic Disorders
Type
article
Field-Weighted Citation Impact
2.64
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article

Bone mineral density in French adults with early-treated phenylketonuria

Manuel Schiff, K. Mazodier, V. Leguy‐Seguin, Sybil Charrière et al.
2 citations
Molecular Genetics and Metabolism
Metabolism and Genetic Disorders
2.64
article

Bone mineral density in French adults with early-treated phenylketonuria

Manuel Schiff, K. Mazodier, V. Leguy‐Seguin, Sybil Charrière, Christian Lavigne, Elisa Dybal, F. Maillot, L. Astudillo, Claire Gay, Alice Kuster, Sylvie Odent, Jean-Baptiste Arnoux, Christel Thauvin-Robinet, Claire Douillard, Vincent Rigalleau, François Feillet, Alain Fouilhoux
article en
2 citations

Abstract

Phenylketonuria (PKU) treatment requires a low-phenylalanine (Phe) diet limiting natural protein intake, using medical low-protein foods and Phe-free amino acids (AA) supplements along with micronutriments' supplies. Current recommendations suggest maintaining this diet for life to prevent neuro-psychological effects of high Phe concentrations. The long-term consequences of such a diet are poorly understood, particularly on bone health. Our study aimed to assess the prevalence of low bone mineral density (BMD) (Z-score ≤ -2, for vertebral and/or femoral site) in adults with PKU and to investigate associated risk factors, in the French ECOPHEN cohort. The study included 171 patients with 67.3 % of women and a median age of 27 years old. The median femoral and vertebral Z-scores of BMD were both - 0.6. Only 11.4 % of patients had a low BMD. Compared to patients with normal BMD, patients with low BMD had a lower body mass index (BMI) (median 20.4 versus 24.4 kg/m<sup>2</sup>, p = 0.002), and were more likely to have never stopped their diet (58.8 % versus 31.8 %, p = 0.029). They also had higher total protein intake (1.1 versus 0.9 g/kg/day, p = 0.015), with more proteins from AA supplements (0.80 vs 0.53 g/kg/day, p = 0.010). In multivariate analysis, younger patients born after 1990 and who never stopped diet had a 4.7 times risk to have low BMD (p = 0.005), after adjustment on age, sex, BMI. In summary, our study identified a subgroup of PKU adult patients with low BMD and showed that prolonged low natural protein diet is associated with low BMD.

Molecular Genetics and MetabolismVol. 144(3)
Université Claude Bernard Lyon 1 (FR), Délégation Paris 5 (FR), Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Bourgogne (FR), Université Paris Cité (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire de Toulouse (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Centre Hospitalier Universitaire de Tours (FR), Hôpital de la Conception (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Bretonneau (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Laboratoire National de Référence (MA), Centre Hospitalier Universitaire d'Angers (FR), Hôpital Nord (FR), CHU Dijon Bourgogne (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Institut de génétique et de développement de Rennes (FR), Hôpital Louis Pradel (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Nutrition-Génétique et Exposition aux Risques Environnementaux (FR), Université de Rennes (FR)
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