Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review

Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review Publisher Pubmed

Van Vliet D¹ ; Van Wegberg AMJ^{1, 2} ; Ahring K³ ; Bikmultanowski M⁴ ; Blau N⁵ ; Bulut FD⁶ ; Casas K⁷ ; Didycz B⁴ ; Djordjevic M⁸ ; Federico A⁹ ; Feillet F¹⁰ ; Gizewska M¹¹ ; Gramer G¹² ; Hertecant JL¹³ Show All Authors

Van Vliet D¹
Van Wegberg AMJ^{1, 2}
Ahring K³
Bikmultanowski M⁴
Blau N⁵
Bulut FD⁶
Casas K⁷
Didycz B⁴
Djordjevic M⁸
Federico A⁹
Feillet F¹⁰
Gizewska M¹¹
Gramer G¹²
Hertecant JL¹³
Hollak CEM¹⁴
Jorgensen JV¹⁵
Karall D¹⁶
Landau Y¹⁷
Leuzzi V¹⁸
Mathisen P¹⁹
Moseley K²⁰
Mungan NO⁶
Nardecchia F¹⁸
Ounap K²¹
Powell KK²²
Ramachandran R²³
Rutsch F²⁴
Setoodeh A²⁵
Stojiljkovic M²⁶
Trefz FK⁵
Usurelu N²⁷
Wilson C²⁸
Van Karnebeek CD^{29, 30}
Hanley WB³¹
Van Spronsen FJ¹

Show Affiliations

1. University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, RB, 9700, Netherlands
2. Department of Gastroenterology, Radboud University Medical Center, Nijmegen, Netherlands
3. Department of PKU, Kennedy Center, Copenhagen University Hospital, Glostrup, Denmark
4. University Children's Hospital, Jagiellonian University, Krakow, Poland
5. Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany
6. Department of Pediatrics, Cukurova University, Faculty of Medicine, Adana, Turkey
7. Medical Genetics, Sanford Health, Fargo, ND, United States
8. Mother and Child Health Care Institute of Serbia Dr Vukan Cupic, School of Medicine, University of Belgrade, Belgrade, Serbia
9. Department of Medical, Surgical and Neurological Sciences, Medical School, University of Siena, Policlinico Santa Maria Alle Scotte, Siena, Italy
10. Department of Pediatrics, Hopital d'Enfants Brabois, CHU Nancy, Vandoeuvre les Nancy, France
11. Dept. of Pediat., Endocrinol., Diabetology, Metab. Diseases and Cardiology of the Developmental Age, Pomeranian Medical University, Szczecin, Poland
12. Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
13. Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates
14. Department of Internal Medicine, Division of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands
15. Department of Pediatrics, Oslo University Hospital, Oslo, Norway
16. Clinic for Pediatrics, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria
17. Metabolic Disease Unit, Sheba Medical Center, Edmond and Lily Safra Children's Hospital, Tel Aviv, Israel
18. Department of Pediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
19. Department of Internal Medicine, Oslo University Hospital, Oslo, Norway
20. Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
21. Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
22. Department of Genetics and Metabolism, Chapel Hill Hospital, University of North Carolina, Chapel Hill, United States
23. Department of Chemical Pathology and Metabolic Medicine, Guys and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
24. Department of General Pediatrics, Muenster University Children's Hospital, Muenster, Germany
25. Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
26. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
27. Institute of Mother and Child, Centre of Reproductive Health and Medical Genetics, Chisinau, Moldova
28. Newborn Metabolic Screening Unit, LabPlus, Auckland City Hospital, Auckland, New Zealand
29. Departments of Pediatrics and Clinical Genetics, Academic Medical Centre, Emma Children's Hospital, Amsterdam, Netherlands
30. Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
31. Clinical and Biochemical Genetics, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada

Source: Orphanet Journal of Rare Diseases Published:2018

Abstract

Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients. © 2018 The Author(s).

Style	Citing Format
MLA	Van Vliet D, et al.. "Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review." Orphanet Journal of Rare Diseases, vol. 13, no. 1, 2018, pp. -.
APA	Van Vliet D, Van Wegberg AMJ, Ahring K, Bikmultanowski M, Blau N, Bulut FD, Casas K, Didycz B, Djordjevic M, Federico A, Feillet F, Gizewska M, Gramer G, Hertecant JL, Hollak CEM, Jorgensen JV, Karall D, Landau Y, Leuzzi V, ... Van Spronsen FJ (2018). Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review. Orphanet Journal of Rare Diseases, 13(1), -.
Chicago	Van Vliet D, Van Wegberg AMJ, Ahring K, Bikmultanowski M, Blau N, Bulut FD, Casas K, et al.. "Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review." Orphanet Journal of Rare Diseases 13, no. 1 (2018): -.
Harvard	Van Vliet D et al. (2018) 'Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review', Orphanet Journal of Rare Diseases, 13(1), pp. -.
Vancouver	Van Vliet D, Van Wegberg AMJ, Ahring K, Bikmultanowski M, Blau N, Bulut FD, et al.. Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review. Orphanet Journal of Rare Diseases. 2018;13(1):-.
BibTex	@article{ author = {Van Vliet D and Van Wegberg AMJ and Ahring K and Bikmultanowski M and Blau N and Bulut FD and Casas K and Didycz B and Djordjevic M and Federico A and Feillet F and Gizewska M and Gramer G and Hertecant JL and Hollak CEM and Jorgensen JV and Karall D and Landau Y and Leuzzi V and Mathisen P and Moseley K and Mungan NO and Nardecchia F and Ounap K and Powell KK and Ramachandran R and Rutsch F and Setoodeh A and Stojiljkovic M and Trefz FK and Usurelu N and Wilson C and Van Karnebeek CD and Hanley WB and Van Spronsen FJ}, title = {Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review}, journal = {Orphanet Journal of Rare Diseases}, volume = {13}, number = {1}, pages = {-}, year = {2018} }
RIS	TY - JOUR AU - Van Vliet D AU - Van Wegberg AMJ AU - Ahring K AU - Bikmultanowski M AU - Blau N AU - Bulut FD AU - Casas K AU - Didycz B AU - Djordjevic M AU - Federico A AU - Feillet F AU - Gizewska M AU - Gramer G AU - Hertecant JL AU - Hollak CEM AU - Jorgensen JV AU - Karall D AU - Landau Y AU - Leuzzi V AU - Mathisen P AU - Moseley K AU - Mungan NO AU - Nardecchia F AU - Ounap K AU - Powell KK AU - Ramachandran R AU - Rutsch F AU - Setoodeh A AU - Stojiljkovic M AU - Trefz FK AU - Usurelu N AU - Wilson C AU - Van Karnebeek CD AU - Hanley WB AU - Van Spronsen FJ TI - Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review JO - Orphanet Journal of Rare Diseases VL - 13 IS - 1 SP - EP - PY - 2018 ER -

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Abstract