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2013 | 60 | 4 | 613-616
Article title

Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness

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Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might require a very expensive trial treatment with BH4 or prolonged BH4-loading procedures. The selection of patients eligible for BH4-therapy by means of genotyping of the PAH gene mutations may be recommended as a complementary approach. A population-wide genotyping study was carried out in 1286 Polish phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover prospectively the treatment by a National Health Fund. A total of 95 types of mutations were identified. Genetic variants corresponding with probable BH4-responsiveness were found in 28.2% of cases. However, patients with mild or classical phenylketonuria who require continuous treatment accounted for 11.4% of the studied population only. Analysis of the published data shows similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe. Therefore, it can be concluded, that the proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region.
Physical description
  • Aulehla-Scholz C, Heilbronner H (2003) Mutational spectrum in German patients with phenylalanine hydroxylase deficiency. Hum Mutat, Mutation in Brief #587.
  • Baranovskaya S, Shevtsov S, Maksimova S, Kuzmin A, Schwartz E (1996) The mutations and VNTRs in the phenylalanine hydroxylase gene of phenylketonuria in St. Petersburg. J Inherit Metab Dis 19: 705.
  • Bercovich D, Elimelech A, Zlotogora J, Korem S, Yardeni T, Gal N (2008) Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene. J Hum Genet 53: 407-418.
  • Bickel H, Bachmann C, Beckers R, Brandt NJ, Clayton BE, Corrado G (1981) Neonatal mass screening for metabolic disorders. Eur J Pediatr 137: 133-139.
  • Bik-Multanowski M, Pietrzyk JJ (2008) Single exon deletions in the PAH gene in Polish PKU patients. Mol Genet Metab 94: 267.
  • Bik-Multanowski M, Pietrzyk JJ, Mozrzymas R (2011) Routine use of CANTAB system for detection of neuropsychological deficits in patients with PKU. Mol Genet Metab 102: 210-213.
  • BIOPKUdb: Database of PKU genotypes investigated for BH4-responsiveness;
  • Blau N, Erlandsen H (2004) The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Mol Genet Metab 82: 101-111.
  • Blau N, van Spronsen FJ, Levy HL (2010) Phenylketonuria. Lancet 376: 1417-1427.
  • Cali F, Ruggeri G, Vinci M, Meli C, Carducci C, Leuzzi V (2010) Exon deletions of the PAH gene in Italian hyperphenylalaninemics. Exp Mol Med 42: 81-86.
  • Charikova EV, Khalchitskii SE, Antoshechkin AG, Schwartz EI (1993) Distribution of some point mutations in the phenylalanine hydroxylase gene of phenylketonuria patients from the Moscow region. Hum Hered 43: 244-249.
  • Christ SE, Huijbregts SC, de Sonneville LM, White DA (2010) Executive function in early-treated phenylketonuria: profile and underlying mechanisms. Mol Genet Metab 99 (Suppl 1): S22-S32.
  • Kadasi L, Polakova H, Ferakova E, Hudecova S, Bohusova T, Szomolayova I (1995) PKU in Slovakia: mutation screening and haplotype analysis. Hum Genet 95: 112-114.
  • Kalaydjieva L, Dworniczak B, Kremensky I, Radeva B, Horst J (1993) Population genetics of phenylketonuria in Bulgaria. Dev Brain Dysfunct 6: 39-54.
  • Kasnauskiene J, Giannattasio S, Lattanzio P, Cimbalistiene L, Kucinskas V (2003) The molecular basis of phenylketonuria in Lithuania. Hum Mutat 21: 398.
  • Kozak L, Blazkova M, Kuhrova V, Pijackova A, Růzickova S, St'astna S (1997) Mutation and haplotype analysis of phenylalanine hydroxylase alleles in classical PKU patients from the Czech Republic: identification of four novel mutations. J Med Genet 34: 893-898.
  • Kure S, Hou DC, Ohura T, Iwamoto H, Suzuki S, Sugiyama N (1999) Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr 135: 375-378.
  • Muntau AC, Roschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP (2002) Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med 347: 2122-2132.
  • Nechiporenko MV, Lalivshits LA (2000) Analysis of mutations in the phenylalanine hydroxylase gene in Ukrainian families at high risk for phenylketonuria. Tsitol Genet 34: 59-63.
  • Smith I, Beasley MG, Ades AE (1991) Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria. Arch Dis Child 66: 311-316.
  • Walter JH, White FJ, Hall SK, MacDonald A, Rylance G, Boneh A (2002) How practical are recommendations for dietary control in phenylketonuria? Lancet 360: 55-57.
  • Zschocke J (2003) Phenylketonuria mutations in Europe. Hum Mutat 21: 345-356.
  • Zurflüh MR, Zschocke J, Lindner M, Feillet F, Chery C, Burlina A (2008) Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Hum Mutat 29: 167-)175.
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