Dynamics of hyperphenylalaninemia and intellectual outcome in teenagers with phenylketonuria

• Authors: Bożena Didycz , Mirosław Bik-Multanowski
• Languages of publication: EN

Abstracts

EN

Insufficient treatment adherence after early childhood is frequently observed in patients with phenylketonuria. Assessment of these individuals' long-term metabolic control could enable early detection of the risk of intellectual deterioration resulting from high blood phenylalanine concentration. However, the predictive value of specific parameters related to individual dynamics of hyperphenylalaninemia is not clear. Here, we assessed the impact of blood phenylalanine fluctuations during the first 12 years of life on cognitive outcome in early and continuously treated teenagers with phenylketonuria. We have analyzed a total of 5141 results of blood phenylalanine measurements in 32 patients. The phenylalanine levels of these patients were usually acceptable during their early childhood, but the control of hyperphenylalaninemia worsened and the average treatment adherence dropped to 40% during the late primary school. Our analysis revealed a strong association between the Wechsler intelligence verbal scores and the mean of the yearly means of phenylalanine concentrations (r=-0.62). The correlations of IQ scores with median phenylalanine concentrations and the variability of blood phenylalanine levels gave weaker associations. The Wechsler verbal scores were also strongly correlated with the treatment adherence level during preschool and late primary school (r=0.61 and 0.72). The mean of the yearly means of blood phenylalanine concentrations appears to be a better predictor of cognitive outcome in children with phenylketonuria than other parameters related to phenylalanine fluctuations. The percentage of acceptable phenylalanine levels below 50-60% should be regarded as a "red flag" due to the risk of intellectual deterioration in patients.

Keywords

EN

inborn error of metabolism; metabolic control of PKU; treatment adherence

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 3
• Pages: 527-531

Dates

published

2017

received

2017-02-08

revised

2017-04-25

accepted

2017-05-15

(unknown)

2017-08-31

Contributors

author

Bożena Didycz

• Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland

author

Mirosław Bik-Multanowski

• Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland

References

• Anastasoaie V, Kurzius L, Forbes P, Waisbren S (2008) Stability of blood phenylalanine levels and IQ in children with phenylketonuria. Mol Genet Metab 95: 17-20. doi: 10.1016/j.ymgme.2008.06.014.
• Bik-Multanowski M, Didycz B, Mozrzymas R, Nowacka M, Kaluzny L, Cichy W, Schneiberg B, Amilkiewicz J, Bilar A, Gizewska M, Lange A, Starostecka E, Chrobot A, Wojcicka-Bartlomiejczyk BI, Milanowski A (2008) Quality of life in noncompliant adults with phenylketonuria after resumption of the diet. J Inherit Metab Dis 31: S415-S418. doi: 10.1007/s10545-008-0978-7.
• Blau N, van Spronsen FJ, Levy HL (2010) Phenylketonuria. Lancet 376: 1417-1427. doi: 10.1016/S0140-6736(10)60961-0.
• Burgard P, Bremer HJ, Buhrdel P, Clemens PC, Monch E, Przyrembel H, Trefz FK, Ullrich K (1997) Rationale for the German recommendations for phenylalanine level control in phenylketonuria. Eur J Pediatr 158: 46-54.
• Flynn JR (1987) Massive IQ gains in 14 nations: What IQ tests really measure. Psychological Bulletin 101: 171-191
• van Spronsen FJ, van Wegberg AM, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Giżewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, Trefz FK, van Rijn M, Walter JH, MacDonald A (2017) Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 5: 743-756. doi: 10.1016/S2213-8587(16)30320-5.
• Viau KS, Wengreen HJ, Ernst SL, Cantor NL, Furtado LV, Longo N (2001) Correlation of age-specific phenylalanine levels with intellectual outcome in patients with phenylketonuria. J Inherit Metab Dis 34: 963-971. doi: 10.1007/s10545-011-9329-1.
• Waisbren S, Noel K, Fahrbach K, Cella C, Frame D, Dorenbaum A, Levy H (2007) Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab 92: 63-70.
• Walter JH, White FJ, MacDonald A (2002) How practical are recommendations for dietary control in phenylketonuria? Lancet 360: 55-57.

Identifiers

DOI

10.18388/abp.2017_1524