Bone Mineral Density in Patients with Phenylketonuria in Iran

Document Type : original article

Authors

1 Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.

2 Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.

4 Maternal, Fetal & Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Background: Factors like low-protein diet may impose Phenylketonuria (PKU) patients to impaired skeletal disease. The present study assessed the status of Bone Mineral Density (BMD) among PKU patients on a low-protein diet.
Methods: A cross-sectional study was conducted (Tehran, Iran, 2019). Patients aged ≥ 4 years old with a definite diagnosis of PKU on a low-protein diet were included. BMD values of the lumbar spine and femoral neck were assessed. The primary objective was assessing femoral and lumbar BMD status in PKU patients.
Results: Forty-one PKU patients entered the study. The mean BMI was 20.712±4.833 Kg/m2. The mean bone age was significantly lower than chronological age (10.9 vs. 12.4 years; P=0.008). The results showed a bone mass reduction in 23.1% of all patients.  A significant correlation was observed between lumbar and femoral BMD values (P=0.001; r=0.516). Most patients (about 77%) had lumbar Z-scores>-1 and 10.3% showed Z-scores in the range of osteoporosis. Age (P=0.004) and age at diagnosis (P=0.002) were the influencing factors on BMD status. The results showed a significantly inverse correlation between BMD lumbar levels with the patient’s chronological age (P=0.016), age of PKU diagnosis (P=0.002), and phenylalanine level (P=0.025)
Conclusion: The results delineated impaired skeletal status among PKU patients on a low-protein diet. Lumbar Z-score values inversely correlated with the patient’s chronological age, age at PKU diagnosis, and phenylalanine level. Hence, early PKU diagnosis and treatment during neonatal period, as well as controlling phenylalanine concentration may improve BMD status.

Keywords

References

  1. van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Phenylketonuria. Nature reviews Disease primers. 2021; 7(1):36.
  2. Morawska A, Mitchell AE, Etel E, Kirby G, McGill J, Coman D, Inwood A. Psychosocial functioning in children with phenylketonuria: Relationships between quality of life and parenting indicators. Child: care, health and development. 2020; 46(1):56-65.
  3. Etemad K, Heidari A, Setoodeh A, Shayeganrad A, Akhlaghi A, Azizi M, Nejatbakhsh R, Beheshti Beglar M, Lotfi M. Health-related quality of life of parents of children with phenylketonuria in Tehran Province, Islamic Republic of Iran. Eastern Mediterranean Health Journal. 2020; 26(3).
  4. de Castro MJ, de Lamas C, Sánchez-Pintos P, González-Lamuño D, Couce ML. Bone status in patients with phenylketonuria: a systematic review. Nutrients. 2020; 12(7):2154.
  5. Demirdas S, van Spronsen FJ, Hollak CE, van der Lee JH, Bisschop PH, Vaz FM, Ter Horst NM, Estela Rubio-Gozalbo M, Bosch AM. Micronutrients, essential fatty acids and bone health in phenylketonuria. Annals of Nutrition and Metabolism. 2017; 70(2):111-21.
  6. Rovelli V, Ercoli V, Dionigi AR, Paci S, Salvatici E, Zuvadelli J, Banderali G. Low bone mineralization in phenylketonuria may be due to undiagnosed metabolic acidosis. Molecular Genetics and Metabolism Reports. 2023; 36:100998.
  7. Tansek MZ, Bertoncel A, Sebez B, Zibert J, Groselj U, Battelino T, Avbelj Stefanija M. Anthropometry and bone mineral density in treated and untreated hyperphenylalaninemia. Endocrine Connections. 2020; 9(7):649-57.
  8. Dobrowolski SF, Tourkova IL, Robinson LJ, Secunda C, Spridik K, Blair HC. A bone mineralization defect in the Pahenu2 model of classical phenylketonuria involves compromised mesenchymal stem cell differentiation. Molecular genetics and metabolism. 2018; 125(3):193-9.
  9. Hansen KE, Ney D. A systematic review of bone mineral density and fractures in phenylketonuria. Journal of Inherited Metabolic Disease: Official Journal of the Society for the Study of Inborn Errors of Metabolism. 2014; 37(6):875-80.
  10. Mojibi N, Ghazanfari-Sarabi S, Hashemi-Soteh SMB. The Prevalence and incidence of congenital phenylketonuria in 59 countries: A systematic review. Journal of pediatrics review. 2021; 9(2):83-96.
  11. Ajami N, Soleimani A, Jafarzadeh‐Esfehani R, Hasanpour M, Rashid Shomali R, Abbaszadegan MR. Mutational landscape of phenylketonuria in Iran. Journal of Cellular and Molecular Medicine. 2023; 27(17):2457-66.
  12. Kanufre VC, Soares RD, Alves MRA, Aguiar MJ, Starling ALP, Norton RC. Metabolic syndrome in children and adolescents with phenylketonuria. Jornal de pediatria. 2015; 91:98-103.
  13. Tolboom N, Cats E, Helders P, Pruijs J, Engelbert R. Osteogenesis imperfecta in childhood: effects of spondylodesis on functional ability, ambulation and perceived competence. European Spine Journal. 2004; 13:108-13.
  14. Modan-Moses D, Vered I, Schwartz G, Anikster Y, Abraham S, Segev R, Efrati O. Peak bone mass in patients with phenylketonuria. Journal of inherited metabolic disease. 2007; 30:202-8.
  15. Pourfarzam M, Zadhoush F. Newborn screening for inherited metabolic disorders; news and views. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2013; 18(9):801.
  16. Fewtrell M. Bone densitometry in children assessed by dual x-ray absorptiometry: uses and pitfalls. Archives of Disease in Childhood. 2003; 88(9):795-8.
  17. Aggarwal A, Northrup H, Rodriguez-Buritica DF, Hashmi SS, Saavedra H. Bone Health in Adults with Phenylketonuria: A Cross-Sectional Study. Journal of Inborn Errors of Metabolism and Screening. 2021; 9.
  18. Coakley KE, Douglas TD, Goodman M, Ramakrishnan U, Dobrowolski SF, Singh RH. Modeling correlates of low bone mineral density in patients with phenylalanine hydroxylase deficiency. Journal of inherited metabolic disease. 2016; 39:363-72.
  19. Barat P, Barthe N, Redonnet-Vernhet I, Parrot F. The impact of the control of serum phenylalanine levels on osteopenia in patients with phenylketonuria. European journal of pediatrics. 2002; 161(12):687.
  20. Demirdas S, Coakley KE, Bisschop PH, Hollak CE, Bosch AM, Singh RH. Bone health in phenylketonuria: a systematic review and meta-analysis. Orphanet journal of rare diseases. 2015; 10(1):1-17.
  21. Lubout CM, Arrieta Blanco F, Bartosiewicz K, Feillet F, Gizewska M, Hollak C, van der Lee JH, Maillot F, Stepien KM, Wagenmakers MAEM, Welsink-Karssies MM, van Spronsen FJ, Bosch AM. Bone mineral density is within normal range in most adult phenylketonuria patients. Journal of Inherited Metabolic Disease. 2020; 43(2):251-8.
  22. Ashe K, Kelso W, Farrand S, Panetta J, Fazio T, De Jong G, Walterfang M. Psychiatric and cognitive aspects of phenylketonuria: the limitations of diet and promise of new treatments. Frontiers in psychiatry. 2019; 10:561.
  23. de Groot MJ, Hoeksma M, van Rijn M, Slart RH, van Spronsen FJ. Relationships between lumbar bone mineral density and biochemical parameters in phenylketonuria patients. Molecular Genetics and Metabolism. 2012; 105(4):566-70.
  24. Barta AG. Phenylketonuria in adulthood: exploring long-term consequences.
  25. Porta F, Mussa A, Zanin A, Greggio NA, Burlina A, Spada M. Impact of metabolic control on bone quality in phenylketonuria and mild hyperphenylalaninemia. Journal of pediatric gastroenterology and nutrition. 2011; 52(3):345-50.
  26. Adamczyk P, Morawiec-Knysak A, Płudowski P, Banaszak B, Karpe J, Pluskiewicz W. Bone metabolism and the muscle–bone relationship in children, adolescents and young adults with phenylketonuria. Journal of bone and mineral metabolism. 2011; 29:236-44.
  27. Stroup BM, Hansen KE, Krueger D, Binkley N, Ney DM. Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study. Molecular genetics and metabolism reports. 2018; 15:30-5.
  28. Clark EM, Ness AR, Bishop NJ, Tobias JH. Association between bone mass and fractures in children: a prospective cohort study. Journal of bone and mineral research. 2006; 21(9):1489-95.
  29. Heidari A, Arab M, Damari B. A policy analysis of the national phenylketonuria screening program in Iran. BMC health services research. 2021; 21(1):1-9.
  30. Davarani ER, Takaloo FM, Daneshi S, Sanjari P, Khanjani N, Hushmandi K, Raei M. Assessing the phenylketonuria (PKU) neonatal screening program and the incidence rates of PKU in Kerman County, Iran: a health system research. Journal of Pediatric and Neonatal Individualized Medicine (JPNIM). 2022; 11(2):e110217-e.
Journal of Pediatric Perspectives
Volume 12, Issue 1
January 2024
Pages 18474-18483

Files

Share

How to cite

Statistics