Neurological assessment of 38 late-diagnosed children with classic phenylketonuria
Amaç: Geç tanı alan fenilketonuri hastalarında manyetik rezonans görüntüleme (MRG), elektroensefalografi (EEG), uyarılmış görsel potansiyeller (VEP) ve zeka katsayısı ile nörolojik açıdan etkilenme ve bu parametrelerin tanı yaşı ve kan fenilalanin düzeyi ile korelasyonu araştırıldı. Gereç ve Yöntem: Çukurova Üniversitesi Tıp Fakültesi, Çocuk Metabolizma ve Beslenme Bilim Dalında başvuran geç tanı almış 38 klasik fenilketonurili hasta çalışmaya alındı. Kan fenilalanin düzeyleri spektroflorometrik yöntem ile ölçüldü. Ankara gelişim tarama envanteri (AGTE), Türk çocuklarına göre uyarlanmış Wechesler zeka testi (WISC-R) yaş gruplarına uygun olarak yapıldı. Tüm çocuklara Türk çocuklarına göre uyarlanmış Porteus Maze zeka testi uygulandı. Tüm çocuklara EEG kaydı yapıldı. Merkezi sinir sisteminin görsel uyaranlara verdiği yanıt VEP ile değerlendirildi. MRG ile santral sinir sistemi bulguları incelendi. Bulgular: Yüksek plazma fenilalanin düzeyi ve geç tanı, düşük zeka katsayısı, patolojik EEG, patolojik VEP ile ilişkili bulundu. Yüksek fenilalanin düzeyi ciddi beyaz cevher sinyal değişiklikleri ile ilişkiliydi. Sonuç: Çalışmamız erken tanının ve tanı anındaki düşük kan fenilalanin düzeyinin entellektüel , nörolojik gelişim ve görme üzerine olan etkisini göstermiştir.
Geç tanı konulan 38 klasik fenilketonurili hastanın nörolojik açıdan değerlendirilmesi
Purpose: We investigated the neurological outcome of 38 late-diagnosed phenylketonuria patients with magnetic resonance imaging (MRI), electroencephalography (EEG), visual evoked potentials (VEP), intelligence quotients (IQ) and examined the correlation of these parameters with the age and the plasma phenylalanine levels of patients at diagnosis. Material and Methods: Thirty-eight late-diagnosed classic phenylketonuria patients were enrolled in the study. Plasma phenylalanine levels were measured by spectrofluorometric method. MRI was evaluated by a pediatric neuroradiologist. Ankara developmental screening inventory (ADSI) and Wechsler intelligence scale for Turkish children (WISC-R) test were performed to detect IQ scores. Porteus Mazo test adapted for Turkish children intelligence test were performed to all children. The EEG of all patients were recorded. VEP was used to measure the electrical activity in the brain to visual stimulus. Results: The high plasma phenylalanine levels and latediagnosis were associated with low IQ scores, pathological EEG, and pathological VEP patterns. High PA levels were also associated with more serious white matter signal abnormalities. Conclusion: Our results demonstrated the impact of early diagnosis and low levels of phenylalanine at diagnosis on the intellectual, neurological development and visual outcomes.
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- Coşkun T, Ozguc M, Tokatlı A, Kalkanoglu HS, Dursun A, Tokol S et al. Phenylketonuria in Turkey: Epidemiological, clinical and genetic aspects. Dev Brain Dysfunct. 1993;6:134-40.
- Scriver CR. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: The Metabolic and Molecular Bases of Inherited Disease, 8th ed (Eds CR Scriver, AL Beaudet, WS Sly , D Valle):1667- 1724. New York, McGraw-Hill. 2001.
- Spronsen FJ, van RM, Bekhof J, Koch R, Smit PG. Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am J Clin Nutr. 2001;73:153-7.
- Surtees R, Blau N. The neurochemistry of phenylketonuria. Eur J Pediatr. 2000;159:109-13.
- Weglage J, Wiedermann D, Moller H, Ullrich K. Pathogenesis of different clinical outcomes in spite of identical genotypes and comparable blood phenylalanine concentrations in phenylketonurics. J Inherit Metab Dis. 1998;21:181-2.
- Weglage J, Wiedermann D, Denecke J, Feldman R, Koch HG, Ullrich K, et al. Individual blood-brain barrier phenylalanine transport determines clinical outcome in phenylketonuria. Ann Neurol. 2001;50:463- 7.
- Pietz B, Kreis R, Schmidt H, Meyding-Lamadè UK, Rupp A, Boesch C. Phenylketonuria: findings at MRI imaging and localized in vivo MR spectroscopy of the brain in patients with early treatment. Radiology. 1996;201: 413-20.
- Ulrich K, Moller H, Weglage J. White matter abnormalities in phenylketonuria: results of magnetic resonance 1994;25:278-9. Acta Paediatr.
- Bick U, Ullrich K, Stöber U, Möller H, Schuierer G, Ludolph AC et al. White matter abnormalities in patients with treated hyperphenylalaninaemia: magnetic resonance relaxometry and proton spectroscopy findings. Eur J Pediatr. 1993;152:1012- 20.
- Leuzzi V, Trasimeni G, Gualdi GF, Antonozzi I. Biochemical, clinical and neuroradiological (MRI) correlation in late-detected PKU patients. J Inherit Metab Dis 1995;18:624-34.
- Henderson RM, Mc Culloch DL, Herbet AM, Robinson PH, Taylor MJ. Visual event-related potentials in children with phenylketonuria. Acta Paediatr. 2000;89:52-7.
- Jones SJ, Turano G, Kriss A, Shawkat F, Kendall B, Thompson AJ. Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state and IQ. J Neurol Neurosurg Psychiatry. 1995;59:260-5.
- Trefz FK, Cipcic-Schmidt S, Koch R. Final intelligence phenylketonuria. Eur J Pediatr. 2000;159:145-8.
- Coskun T, Topcu M, Ustundag I, Ozalp I, Renda Y, Ciger A. Neurophysiological studies of patients with classical phenylketonuria: evaluating of results of IQ scores, EEG and evoked potentials. Turk J Pediatr. 1993;356:1-10.
- Ullrich K, Weglage J, Schuierer G. Cranial MRI in PKU: evaluation of a critical threshold for blood phenylalanine. Neuropediatrics 1994;25:278-9.
- Pietz J, Lutcke A, Sontheimer D, Benninger C, Pietze B,Batzler U. EEG development in early-treated PKU patients from birth to years of age. Eur J Pediatr. 1990;149:28-33.
- Van der Knaap MS, Valk J . Phenylketonuria In: Magnetic resonance of myelination and myelin disorders. 2nd ed (Eds MS Van der Knaap ,J Valk ) :Berlin, Springer. 2005:284-293.
- Leuzzi V, Tosetti M, Montanaro D. The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1 H MRS) study. J Inherit Metab Dis. 2007;30:209-16.
- Huttenlocher . The neuropathology of phenylketonuria: human and animal studies. Eur J Pediatr. 2000;159:102-6.
- Koch R, Verma S, Gilles FH. Neuropathology of a 4-month-old infant born to a woman with phenylketonuria. Dev Med Child Neurol. 2008;50:230-33.
- Cleary MA, Walter JH, Wrath JE, Jenkins JP, Alani SM, Tyler K. Magnetic resonance imaging of the brain in phenylketonuria. Lancet. 1994;344:87-90.
- Thompson AJ, Tillotson S, Smith I. Brain MRI changes in phenylketonuria associations with dietary status. Brain. 1993;116:811-21.
- Waisbren SE, Noel K, Fahrbach K, Cella C, Frame D, Dorenbaum A, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria:A systematic review and meta-analysis. Mol. Genet. Metab. 2007;92:63-70.
- Rolle-Daya H, Pueschel SM, Lombroso CT. Electroencephalographic findings in children with phenylketonuria. AM J Dis Child. 1975;129:896-900.
- Gross PT, Berlow S, Schuett VE, Fariello RG. EEG in phenylketonuria: Attempt to establish clinical importance of EEG changes Arch of Neurol. 1981;38:122-6.
- Karimzadeh P, Alaee MR, Zarafshan H. The association between EEG abnormality and Behavioral disorder:developmental delay in phenylketonuria. ISRN Pediatr. 2012;2012:976206 PMC.Web.( 13 July 2015).