Betül MAZLUM, Banu ANLAR, Şeniz ÖZUSTA, Kader KARLI-OĞUZ, H. Serap KALKANOĞLU-SİVRİ, Fatih ÜNAL

A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood

SUMMARY: Mazlum B, Anlar B, Kalkanoğlu-Sivri HS, Karlı-Oğuz K, Özusta Ş,Ünal F. A late-diagnosed case presenting with autism spectrum disorder inearly childhood. Turk J Pediatr 2016; 58: 318-322.Phenylketonuria is one of the most prevalent autosomal recessive hereditarydisorders in Turkey. If untreated, it results in severe brain damage and canalso be associated with autism in certain patients. We present a three-year oldboy who exhibited the symptoms of autism and was subsequently diagnosedwith phenylketonuria. This case illustrates that because the majority ofautism cases are idiopathic, an occasional patient with a metabolic disordermight be overlooked especially in the era of newborn screening. We alsodiscuss the possible pathogenetic processes leading to autistic symptomsin phenylketonuria, and wish to draw attention to the possibility of casesmissed in the screening program because of less than 100% coverage orinsufficient food intake before blood sampling. Clinicians should keep in mindthe possibility of treatable disorders in children with autism even when suchdisorders appear unlikely.

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1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing, 2013.
2. Kim YS, Leventhal BL, Koh YJ, et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 2011; 168: 904-912.
3. Elsabbagh M, Divan G, Koh YJ, et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res 2012; 5: 160-179.
4. Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalence of parentreported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012. Natl Health Stat Report 2013: 1-11.
5. Özalp İ, Coşkun T, Tokatlı A, et al. Neonatal PKU screening in Turkey: 7 years experience in a developing country. Screening 1995; 4: 139-147.
6. Page T. Metabolic approaches to the treatment of autism spectrum disorders. J Autism Dev Disord 2000; 30: 463-469.
7. Zecavati N, Spence SJ. Neurometabolic disorders and dysfunction in autism spectrum disorders. Curr Neurol Neurosci Rep 2009; 9: 129-136.
8. Baieli S, Pavone L, Meli C, Fiumara A, Coleman M. Autism and phenylketonuria. J Autism Dev Disord 2003; 33: 201-204.
9. American Psyciatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSMIV). Washington, DC: American Psychiatric Association, 1994.
10. Blumenfeld CM, Wallace MJ, Anderson R. Phenylketonuria-the guthrie screening test-a method of quantitation, observations on reliability and suggestions for improvement. Calif Med 1966; 105: 429-434.
11. Yalaz K, Vanli L, Yilmaz E, Tokatli A, Anlar B. Phenylketonuria in peidatric neurology practice: A series of 146 cases. J Child Neurol 2006; 21: 987-990.
12. Lowe TL, Tanaka K, Seashore MR, Young JG, Cohen DJ. Detection of phenylketonuria in autistic and psychotic children. JAMA 1980; 243: 126-128.
13. Anderson PJ, Wood SJ, Francis DE et al. Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities. Dev Med Child Neurol 2004; 46: 230- 238.
14. Atalar MH. Evaluation of white matter abnormalities with diffusion-weighted imaging in a boy with classical phenylketonuria: A case report. Kafkas J Med Sci 2013; 3: 145-148.
15. Christ SE, Moffitt AJ, Peck D. Disruption of prefrontal function and connectivity in individuals with phenylketonuria. Mol Genet Metab 2010; 99 (Suppl 1): S33-S40.
16. Kono K, Okano Y, Nakayama K, et al. Diffusionweighted MR imaging in patients with phenylketonuria: relationship between serum phenylalanine levels and ADC values in cerebral white matter. Radiology 2005; 236: 630-636.
17. Moritani T, Smoker WR, Sato Y, Numaguchi Y, Westesson PL. Diffusion-weighted imaging of acute excitotoxic brain injury. AJNR Am J Neuroradiol 2005; 26: 216-228.
18. Diamond A. Consequences of variations in genes that affect dopamine in prefrontal cortex. Cereb Cortex 2007; 17(Suppl 1): i161-i170.
19. Glushakow AV, Dennis DM, Sumners C, Seubert CN, Martynyuk AE. L-phenylalanine selectively depresses currents at glutamatergic excitatory synapses. J Neurosci Res 2003; 72: 116-124.