Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 12, 2020

Delayed phenylketonuria diagnosis: a challenging case in child psychiatry

Aspasia E. Serdari, Christina Zompola and Athanasios Evangeliou



Phenylalanine hydroxylase deficiency is an autosomal recessive inborn error of phenylalanine metabolism.

What is new?

Εven in cases with negative newborn screening for inborn errors of metabolism, the possibility of a metabolic disorder including PKU should be considered in any child presenting symptoms of developmental disorders. Late diagnosed PKU patients require a more specialized and individualized management than if they were early treatment cases.

Case presentation

We discuss a case of a child with typical autistic symptomatology, in whom years later a diagnosis of phenylketonuria was set, even neonatal screening was negative. Τhe patient was placed on a phenylalanine-restricted diet. After a period of clinical improvement, severe behavioral problems with aggressiveness and anxiety were presented. Less restrictive diet ameliorated the symptomatology.


This case highlights the major medical importance of adequate newborn screening policy, in order to avoid missed diagnosed cases. PKU may be presented as autism spectrum disorder. Dietary management needs individualized attentive monitoring.

Corresponding author: Aspasia E. Serdari, MD, Assistant Professor Department of Child and Adolescent Psychiatry, Democritus University of Thrace, Medical School, University Hospital of Alexandroupolis, Dragana, Alexandroupolis68100, Greece, Phone: +302551030407, Fax +302551030491, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. BIOPKU. Available from: in Google Scholar

2. Loukas, YL, Soumelas, GS, Dotsikas, Y, Georgiou, V, Molou, E, Thodi, G, et al.. Expanded newborn screening in Greece: 30 months of experience. J Inherit Metab Dis 2010;3:S341–8. 33 Suppl Epub 2010 Aug 19. PMID: 20721692.Search in Google Scholar

3. Vockley, J, Andersson, HC, Antshel, KM, Braverman, NE, Burton, BK, Frazier, DM, et al.. American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med 2014;16:188–200. Epub 2013 Oct 10. Erratum in: Genet Med. 2014 Apr;16(4):356. PMID: 24385074.Search in Google Scholar

4. Chen, S, Zhu, M, Hao, Y, Feng, J, Zhang, Y. Effect of delayed diagnosis of phenylketonuria with imaging findings of bilateral diffuse symmetric white matter lesions: a case report and literature review. Front Neurol 2019;10:1040. PMID: 31636599; PMCID: PMC6788382.Search in Google Scholar

5. Liu, Y, Dong, Z, Yu, S. Late-diagnosed phenylketonuria mimicking x-linked adrenoleukodystrophy with heterozygous mutations of the PAH Gene: a case report and literature review. Clin Neurol Neurosurg 2018;171:151–5. Epub 2018 Jun 11. PMID: 29909188.Search in Google Scholar

6. van Wegberg, AMJ, MacDonald, A, Ahring, K, Bélanger-Quintana, A, Blau, N, Bosch, AM, et al.. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis 2017;12:162. PMID: 29025426; PMCID: PMC5639803.Search in Google Scholar

7. Gizewska, M, Cabalska, B, Cyrytowski, L, Nowacki, P, Zekanowski, C, Walczak, M, et al.. Different presentations of late-detected phenylketonuria in two brothers with the same R408W/R111X genotype in the PAH gene. J Intellect Disabil Res 2003;47:146–52. PMID: 12542580.Search in Google Scholar

8. Holtzman, C, Slazyk, WE, Cordero, JF, Hannon, WH. Descriptive epidemiology of missed cases of phenylketonuria and congenital hypothyroidism. Pediatrics 1986;78:553–8.10.1542/peds.78.4.553Search in Google Scholar

9. Webster, D. Quality performance of newborn screening systems: strategies for improvement. J Inherit Metab Dis 2007;30:576–84. in Google Scholar

10. Wall, TC, Brumfield, CG, Cliver, SP, Hou, J, Ashworth, CS, Norris, MJ. Does early discharge with nurse home visits affect adequacy of newborn metabolic screening? J Pediatr 2003;143:213–18. in Google Scholar

11. Mazlum, B, Anlar, B, Kalkanoğlu-Sivri, HS, Karlı-Oğuz, K, Özusta Ş, ÜF. A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. Turk J Pediatr 2016;58:318–22. PMID: 28266201.Search in Google Scholar PubMed

12. Erlich, KJ. Case report: neuropsychiatric symptoms in PKU disease. J Pediatr Health Care 2019;33:718–21. Epub 2019 Mar 29. PMID: 30930161.Search in Google Scholar PubMed

13. Manta-Vogli, PD, Dotsikas, Y, Loukas, YL, Schulpis, KH. The phenylketonuria patient: a recent dietetic therapeutic approach. Nutr Neurosci 2018;25:1–12. Epub ahead of print. PMID: 30359206.Search in Google Scholar PubMed

14. Singh, RH, Cunningham, AC, Mofidi, S, et al.. Updated, web-based nutrition management guideline for PKU: an evidence and consensus based approach. Mol Genet Metab 2016;118:72–83. in Google Scholar PubMed

15. Abadie, V, Berthelot, J, Feillet, F, et al.. Consensus national sur la prise en charge des enfants dépistés avec une hyperphénylalaninémie Management of phenylketonuria and hyperphenylalaninemia: the French guidelines. Arch Pediatr 2005;12:594–601. in Google Scholar PubMed

16. Iakovou, KK, Schulpis, K. The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life. J Pediatr Endocrinol Metab 2020;33:95–8. PMID: 31811806.Search in Google Scholar PubMed

Received: 2020-05-05
Accepted: 2020-08-27
Published Online: 2020-11-12
Published in Print: 2021-01-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Scroll Up Arrow