Although delayed developmental milestones were observed in our patients mostly due to delay in age of diagnosis, a phenylalanine restricted diet was introduced immediately after diagnosis as it may reduce the burden of disabilities even at a late stage [32-34]. In conclusion, a compromised bone mineral density was detected at baseline and follow-up study in our patients; potential contributing factors include dietary deficiency of protein, calcium, vitamin D or trace elements or a primary defect in bone turnover inherent to the disease itself; our data do not favour any one particular factor. We suggest further large-scale studies to illustrate the mechanism of low BMD in PKU patients together with annual follow-up DEXA for early detection and treatment to prevent osteoporosis and decrease the risk of fractures later in life. Moreover, and since low BMD was detected both at baseline and follow-up studies, we recommend the importance of searching for new emerging therapies such as enzyme substitution or gene therapy since low protein diet compliance was not sufficient to maintain normal bone mineral density. R e f e r e n c e s 1. Kahler SG, Fahey MC. Metabolic disorders and mental retardation. Am J Med Genet 2003; 117: 31-41. 2. Allen JR, Humphries IR, Waters DL, et al. Decreased bone mineral density in children with phenylketonuria. Am J Clin Nutr 1994; 59: 419-22. 3. Shaw NJ. Osteoporosis in pediatrics. Arch Dis Child Educ Pract 2007; 92: 169-75. 4. Greeves LG, Carson DJ, Magee A, Patterson C. Fractures and phenylketonuria. Acta Paediatr 1997; 86: 242-4. 5. Al-Qadreh A, Schulpis KH, Athanasopoulou H, Mengreli C, Skarpalezou A, Voskaki I. Bone mineral status in children with phenylketonuria under treatment. Acta Paediatr 1998; 87: 1162-6. 6. Barat P, Barthe N, Redonnet-Vernhet I, Parrot F. The impact of the control of serum phenylalanine levels on osteopenia in patients with phenylketonuria. Eur J Pediatr 2002; 161: 687-8. 7. Carson DJ, Greeves LG, Sweeney LE, Crone MD. Osteo- penia and phenylketonuria. Pediatr Radiol 1990; 20: 598-9. 8. Hillman L, Schlotzhauer C, Lee D, et al. Decreased bone mineralization in children with phenylketonuria under treatment. EurJ Pediatr 1996; 155 (Suppl I): S148-52. 9. McMurry MP, Chan GM, Leonard CO, Ernst SL. Related bone mineral status in children with phenylketonuria- relationship to nutritional intake and phenylalanine control. Am J Clin Nutr 1992; 55: 997-1004. 10. Pérez-Duen~as B, Cambra FJ, Vilaseca MA, Lambruschini N, Campistol J, Camacho JA. New approach to osteopenia in phenylketonuric patients. Acta Paediatr 2002; 91: 899-904. 11. Schwahn B, Mokov E, Scheidhauer K, Lettgen B, Scho- nau E. Decreased trabecular bone mineral density in pa- tients with phenylketonuria measured by peripheral quan- titative computed tomography. Acta Paediatr 1998; 87: 61-3. Bone mineral density in patients with phenylketonuria 12. Zeman J, Bayer M, Stepán J. Bone mineral density in patients with phenylketonuria. Acta Paediatr 1999; 88: 1348-51. 13. Modan-Moses D, Vered I, Schwartz G, et al. Peak bone mass in patients with phenylketonuria. J Inherit Metab Dis 2007; 30: 202-8. 14. Virginia E. Schnett. Low protein cookery for phenyl- ketonuria. 3rd ed. University of Wisconin 1997; 43-478. 15. Rutter M. Nature, nurture, and development: from evangelism through science toward policy and practice. Child Dev 2002; 73: 1-21. 16. Seidell JC, Doak CM, de Munter JS, Kuijper LD, Zonne- veld C. Cross sectional growth references and implications for the development of an international growth standard for school-aged children and adolescents. Food Nutr Bull 2006; 27 (Suppl Growth Standard): S189-98. 17. Abd ElBaky A, Ismail N, Salama E, Abou-Zekri M, Fatouh A, Ragab R. Inappropriate restriction of dietary gluten and associated bone acquisition and bone density in Egyptian children with coeliac disease. Arch Med Sci 2009; 5: 589-95. 18. Ward LM, Glorieux FH. The spectrum of pediatric osteoporosis. In: Glorieux FH, Pettifor JM, Jüppner H (eds.). Pediatric bone: biology and diseases. San Diego, CA: Academic Press 2003; 401-42. 19. Cowell CT, Lu PW, Lloyd-Jones SA, et al. Volumetric bone mineral density – a potential role in paediatrics. Acta Pediatr Suppl 1995; 411: 12-6. 20. Przyrembel H, Bremer HJ. Nutrition, physical growth, and bone V density in treated phenylketonuria. EurJ Pediatr 2000; 159 (Suppl 2): S129-135. 21. Campistol J, Vilaseca MA, Cambra J, Lambruschini N. Diagnostico, tratamient o y seguimient o de las hiper- fenilalaninemias. Act Nutr 1998; 24: 22-9. 22. Schulz B, Bremer HJ. Nutrient intake and food consumption of adolescents and young adults with phenylketonuria. Acta Pediatr 1995; 84: 743-8. 23. Aoki K, Ohwada M, Kitagawa TJ. Long-term follow-up study of patients with phenylketonuria detected by the newborn screening programme in Japan. Inherit Metab Dis 2007; 30: 608-13. 24. Dobbelaere D, Michaud L, Debrabander A, et al. Evaluation of nutritional status and pathophysiology of growth retardation in patients with phenylketonuria. J Inherit Metab Dis 2003; 26: 1-6. 25. Schafer F, Burgard P, Batzler U, et al. Growth and skeletal maturation in children with phenylketonuria. Acta Paediatr 1994; 83: 534-41. 26. Van der Schot LW, Doesburg WH, Sengers WCA. The phenylalanine response curve in relation to growth and mental development in the first years of life. Acta Paediatr 1994; 407: 68-9. 27. Verkerk PH, van Spronsen FJ, Smit GPA, Sengers RCA. Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. Arch Dis Child 1994; 71: 114-8. 28. Allen JR, Baur LA, Waters DL, et al. Body protein in prepubertal children with phenylketonuria. Eur J Clin Nutr 1996; 50: 178-86. 29. Dhondt JL, Largillie`re C, Moreno L, Farriaux JP. Physical growth in patients with phenylketonuria. 32nd Annual Symposium of the Society for the Study of Inborn Errors of Metabolism, Edinburgh (Abstract) 1994. 30. Acosta PB, Yannicelli S, Marriage B, et al. Nutrient intake and growth of infants with phenylketonuria undergoing therapy. J Pediatr Gastroenterol Nutr 1998; 27: 287-91. 31. Arnold GL, Vladutiu CJ, Kirby RS, Blakely EM, DeLuca JM. Protein insufficiency and linear growth restriction in phenylketonuria. J Pediatr 2002; 141: 243-6. Arch Med Sci 3, June / 2011 499