Clinical research A long-term study of bone mineral density in patients with phenylketonuria under diet therapy Hala M. Koura1, Nagwa Abdallah Ismail1, Ashraf F. Kamel1, Azza M. Ahmed1, Amal Saad-Hussein2, Laila K. Effat3 1Department of Pediatric, National Research Centre, Cairo, Egypt 2Department of Environmental Research, National Research Centre, Cairo, Egypt 3Department of Molecular Genetic, National Research Centre, Cairo, Egypt Submitted: 7 September 2010 Accepted: 5 December 2010 Arch Med Sci 2011; 7, 3: 493-500 DOI: 10.5114/aoms.2011.23417 Copyright © 2011 Termedia & Banach A b s t r a c t Introduction: Dietary control of classic phenylketonuria (PKU) needs restriction of natural proteins; adequate protein intake is achieved by adding low phenylalanine (phe) formulae. The adequacy of this diet for normal bone mineralization had not been sufficiently evaluated. Our aim was to evaluate and follow up bone mineral density (BMD) in children and adolescents with PKU within a 2-year time interval to assess the adequacy of a phenylalanine restricted diet for bone mineralization and to search for a possible relationship between BMD, dietary control and blood phenylalanine (phe) concentrations. Material and methods: Thirty-two patients with classic PKU (3-19 years) were evaluated for their bone mineral status using dual energy X-ray absorptiometry (DEXA) both at the beginning (baseline) and the end (follow-up) of the study. Results: Low BMD was detected in 31.25% at the start and in 6.25% of patients after 2 years follows-up. No relationship was found between BMD and the duration of diet compliance and phe level as well. Conclusions: In this study the low BMD detected in our patients was both at baseline and follow-up independent of diet restriction. A yearly DEXA would be highly beneficial for early detection and treatment, thus preventing osteoporosis and decreasing the risk of fractures. We also suggest the importance of searching for new emerging therapies such as enzyme substitution or gene therapy as low protein diet compliance was not enough to maintain normal bone mineral density. Key words: phenylketonuria, osteoporosis, bone mineral density, diet. Introduction Phenylketonuria (PKU) is one of the first characterized metabolic diseases. Untreated PKU leads to mental retardation. Classical PKU results from impaired activity of the liver enzyme phenylalanine hydroxylase, which converts phenylalanine (phe) to tyrosine [1]. The advent of neonatal screening for PKU has enabled the start of a low phenylalanine diet early in life and the prevention of intellectual retardation associated with the disease [2]. Osteoporosis is increasingly being recognized in paediatric practice as a consequence of several factors including the increasing complexity of chronic conditions [3]. Several studies have suggested an increased risk of fractures [4] or a defect in bone mineralization in adults, adolescents and children with PKU [2, 5-13]. Corresponding author: Hala M. Koura MD Pediatric Department National Research Centre El-Tahrir Street, Dokki, Egypt Phone +20226706317, Fax: +202 33370931 E-mail: Hala_koura@yahoo.com