Delayed phenylketonuria diagnosis: a challenging case in child psychiatry
-
Aspasia E. Serdari
,
Christina Zompola
Abstract
Objectives
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.
Conclusion
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.
Research funding: None declared.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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.
References
1. BIOPKU. Available from: http://www.biopku.org.Suche 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. https://doi.org/10.1007/s10545-010-9181-8. 33 Suppl Epub 2010 Aug 19. PMID: 20721692.Suche 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. https://doi.org/10.1038/gim.2013.157 Epub 2013 Oct 10. Erratum in: Genet Med. 2014 Apr;16(4):356. PMID: 24385074.Suche 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. https://doi.org/10.3389/fneur.2019.01040 PMID: 31636599; PMCID: PMC6788382.Suche 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. https://doi.org/10.1016/j.clineuro.2018.06.009 Epub 2018 Jun 11. PMID: 29909188.Suche 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. https://doi.org/10.1186/s13023-017-0685-2 PMID: 29025426; PMCID: PMC5639803.Suche 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. https://doi.org/10.1046/j.1365-2788.2003.00449.x PMID: 12542580.Suche 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.78.4.553Suche in Google Scholar
9. Webster, D. Quality performance of newborn screening systems: strategies for improvement. J Inherit Metab Dis 2007;30:576–84. https://doi.org/10.1007/s10545-007-0639-2.Suche 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. https://doi.org/10.1067/S0022-3476(03)00247-6.Suche 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. https://doi.org/10.24953/turkjped.2016.03.016 PMID: 28266201.Suche in Google Scholar PubMed
12. Erlich, KJ. Case report: neuropsychiatric symptoms in PKU disease. J Pediatr Health Care 2019;33:718–21. https://doi.org/10.1016/j.pedhc.2019.02.007 Epub 2019 Mar 29. PMID: 30930161.Suche 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. https://doi.org/10.1080/1028415X.2018.1538196 Epub ahead of print. PMID: 30359206.Suche 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. https://doi.org/10.1016/j.ymgme.2016.04.008.Suche 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. https://doi.org/10.1016/j.arcped.2005.02.004.Suche 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. https://doi.org/10.1515/jpem-2019-0384 PMID: 31811806.Suche in Google Scholar PubMed
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review Articles
- Association between muscle strength and risk factors for metabolic syndrome in children and adolescents: a systematic review
- Adverse effects of metabolic disorders in childhood on adult reproductive function and fertility in the male
- Original Articles
- Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk
- Anthropometric indices and cardiometabolic risk factors in a Ghanaian adolescent population
- Effectiveness of basal LH in monitoring central precocious puberty treatment in girls
- Combination of sleep duration, TV time and body mass index is associated with cardiometabolic risk moderated by age in youth
- Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty
- Training using a simulation-based workshop reduces inaccuracies in estimations of testicular volume
- Longitudinal 15-year follow-up of women with former early puberty: abnormal metabolic profiles not associated with earlier age at onset of puberty, but associated with obesity
- Prenatal smoke exposure is associated with increased anogenital distance in female infants: a prospective case–control study
- Evaluation of the efficiency of serum biotinidase activity as a newborn screening test in Turkey
- Characterization and outcome of 11 children with non-diabetic ketoacidosis
- Challenges of following patients with inherited metabolic diseases during the COVID-19 outbreak. A cross-sectional online survey study
- The utility of 68Ga-DOTATATE PET/CT in localizing primary/metastatic pheochromocytoma and paraganglioma in children and adolescents – a single-center experience
- Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience
- Case Reports
- Delayed phenylketonuria diagnosis: a challenging case in child psychiatry
- Late diagnosis of 3β-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene
- Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion
- Ectopic ACTH production by thymic and appendiceal neuroendocrine tumors – two case reports
- New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19
Artikel in diesem Heft
- Frontmatter
- Review Articles
- Association between muscle strength and risk factors for metabolic syndrome in children and adolescents: a systematic review
- Adverse effects of metabolic disorders in childhood on adult reproductive function and fertility in the male
- Original Articles
- Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk
- Anthropometric indices and cardiometabolic risk factors in a Ghanaian adolescent population
- Effectiveness of basal LH in monitoring central precocious puberty treatment in girls
- Combination of sleep duration, TV time and body mass index is associated with cardiometabolic risk moderated by age in youth
- Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty
- Training using a simulation-based workshop reduces inaccuracies in estimations of testicular volume
- Longitudinal 15-year follow-up of women with former early puberty: abnormal metabolic profiles not associated with earlier age at onset of puberty, but associated with obesity
- Prenatal smoke exposure is associated with increased anogenital distance in female infants: a prospective case–control study
- Evaluation of the efficiency of serum biotinidase activity as a newborn screening test in Turkey
- Characterization and outcome of 11 children with non-diabetic ketoacidosis
- Challenges of following patients with inherited metabolic diseases during the COVID-19 outbreak. A cross-sectional online survey study
- The utility of 68Ga-DOTATATE PET/CT in localizing primary/metastatic pheochromocytoma and paraganglioma in children and adolescents – a single-center experience
- Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience
- Case Reports
- Delayed phenylketonuria diagnosis: a challenging case in child psychiatry
- Late diagnosis of 3β-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene
- Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion
- Ectopic ACTH production by thymic and appendiceal neuroendocrine tumors – two case reports
- New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19
