Present Opportunities for Treatment of Hyperphenylalaninemia
Authors:
D. Procházková
Authors‘ workplace:
Pediatrická klinika, Lékařská fakulta Masarykovy univerzity a Fakultní nemocnice Brno
přednosta prof. MUDr. Z. Doležel, CSc.
Published in:
Čes-slov Pediat 2010; 65 (7-8): 452-458.
Category:
Review
Overview
Phenylketonuria (PKU) is a hereditary disease in the metabolism of the phenylalanine aminoacid, caused by a deficit of phenylalanine hydroxylase in liver. Patients with PKU must maintain an all-life low protein diet with low phenylalanine content in food in the aim to prevent neurological damage. Adherence to the diet is often low due to bad organoleptic properties of the mixtures of aminoacids without phenylalanine as well as the low protein products. The progress in biochemistry, genetics and especially molecular genetics recently resulted in changes of therapeutic strategy in patients with PKU.
The present paper discusses the low protein diet, neutral long chain aminoacids, DHA and EPA, therapeutic postnatal repopulation of liver cells, tratrahydrobiopterin, enzyme replacement therapy by means of phenylalanine ammonia lyase (PAL) and gene therapy as a possible treatment of PKU.
Key words:
hyperphenylalaninemia, phenylketonuria, therapy, low protein diet, neutral long-chain aminoacids – LNAA, glycomacropeptide, GMP, long-chain fatty acids, DHA, EPA, therapeutic postnatal repopulation of liver cells, tetrahydrobiopterin – BH4, phenylalanine ammonia lyase – PAL, gene therapy
Sources
1. Čechák P, Hejcmanová L, Procházková D, et al. Výsledky screeningu hyperfenylalaninémií v českých zemích v letech 1970–2000. Čes.-slov. Pediat. 2001; 56: 667–670.
2. Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol. Genet. Metab. 2007; 92: 63–70.
3. Christ SE, Huijbregts SCJ, de Sonneville LMJ, et al. Executive function in early-treated phenylketonuria: Profile and underlying mechanisms. Mol. Genet. Metabol. 2010; 99: 22–32.
4. Főlling A. Uber Ausscheidung von Phenylbrenztraubensaure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezilitat. Hoppe Seylers Z. Physiol. Chem. 1934; 277: 169–176.
5. Penrose LS, Quastel JH. Metabolic studies in phenylketonuria. Biochem. J. 1937; 31: 266–271.
6. Jervis GA. Phenylpyruvic oligophrenia: deficiency of phenylalanine oxidising system. Proc. Soc. Exp. Biol. Med .1953; 82: 514.
7. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963; 32: 318–343.
8. Kaufman S. The structure of phenylalanine hydroxylation cofactor. Proc. Natl. Acad. Sci. 1963; 50: 1085.
9. Danks DM., Bartholomé K, Clayton BE, et al. Malignant hyperphenylalaninaemia – current status. J. Inherit. Metab. Dis. 1977; 1: 49–53.
10. Woo SLC, Lidsky AS, Güttler F. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature 1983; 306: 151–155.
11. Muntau AC, Rőschinger W, Habich M, et al. Tetrahydrobiopterin as a alternative treatment for mild phenylketonuria. N. Engl. J. Med. 2002; 347: 2122–2132.
12. Gersting SW, Kemter KF, Staudigl M, et al. Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. Am. J. Hum. Genet. 2008; 83: 5–17.
13. Pey AL, Stricher F, Serrano L, et al. Predicted effects of missense mutations on native-state stability account for phenotypic outcome of phenylketonuria, a paradigm misfolding diseases. Am. J. Hum. Genet. 2007; 81: 1006–1024.
14. Holand K. Inherited disorders affecting dopamine and serotonin: Critical neurotransmitters derived from aromatic amino acids. J. Nutr. 2007; 137: 1568–1572.
15. Blau N, Belanger-Quintana A, Demirkol M, et al. Management of phenylketonuria in Europe: survey results from 19 countries. Mol. Genet. Metab. 2010; 99: 109–115.
16. Weglage J, Wiedermann D, Denecke J, et al. Individual blood-brain barier phenylalanine transport in siblings with clasiccal phenylketonuria. J. Inherit. Metab. Dis. 2002; 25: 431–436.
17. Burgard P, Rupp A, Konecki DS, et al. Phenylalaninehydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria. Eur. J. Pediatr. 1996; 155: 11–15.
18. Scriver CR. The PAH gene, phenylketonuria, and a paradigm shift. Hum. Mutat. 2007; 28: 831–845.
19. Bickel H, Gerrard J, Hickmans EM. Influence of phenylalanine intake on the chemistry and behaviour of a phenylketonuric child. Acta Pediatr. 1954; 43: 64.
20. Procházková D, Konečná P, Kolbová L, et al. Fenylketonurie v dospělosti. Čes.-slov. Pediat. 2008; 63: 601–605.
21. Procházková D, Konečná P, Kozák L, et al. Maternální PKU v regionu Moravy. Čes.-slov. Pediat. 2005; 60: 251–256.
22. Pietz J, Kreis R, Rupp A, et al. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J. Clin. Invest. 1999; 103: 1169–1178.
23. Matalon R, Michals-Matalon K, Bhatia G, et al. Large neutral amino acids in the treatment of phenylketonuria (PKU). J. Inherit. Metab. Dis. 2006; 29: 732–738.
24. Rocha JC, Martel F. Large neutral amino acids supplementation in phenylketonuric patients. J. Inherit. Metab. Dis. 2009; 32: 472–480.
25. Ney DM, Gleason ST, van Calcar SC, et al. Nutritional management of PKU with glycomacropeptide from cheese whey. J. Inherit. Metab. Dis. 2009; 32: 32–39.
26. Koletzko B, Beblo S, Demmelmair H, et al. Does dietary DHA improve neural function in children? Observations in phenylketonuria. Prostaglandins Leukot. Essent. Fatty Acids 2009; 80: 159–164.
27. Vajro P, Strisciulio P, Houssin D, et al. Correction of phenylketonuria after liver transplantation in a child with cirrhosis. N. Engl. J. Med. 1993; 329: 363.
28. Harding CO, Ding Z, Thöny B. Gene and cell therapies for phenylketonuria (PKU). In: Blau N. PKU and BH4-Advances in Phenylketonuria and Tetrahydrobiopterin. Heilbronn: SPS Verlagsgesellschaft, 2006: 321–349.
29. Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding afinity (increased K (m)): relevance to genetic disease and polymorphism. Am. J. Clin. Nutr. 2002; 75: 616–658.
30. Dobrowolski SF, Borski K, Ellingson CC, et al. A limited spektrum of phenylalanine hydroxylase mutations is observed in phenylketonuria patients in western Poland and implications for treatment with 6R tetrahydrobiopterin. J. Hum. Genet. 2009; 54: 335–339.
31. Hennermann JB, Bührer Ch, Blau N, et al. Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. Mol. Genet. Metab. 2005; 86: 86–90.
32. Burlina A, Blau N. Effect of BH4 supplementation on phenylalanine tolerance. J. Inherit. Metab. Dis. 2009; 32: 40–45.
33. Singh RH, Jurecki E, Rohr F. Recommendations for personalized dietary adjustments based on patient response to tetrahydrobiopterin (BH4) in phenylketonuria. Top. Clin. Nutr. 2008; 23: 149–157.
34. Sarkassian ChN, Gamez A, Wang L, et al. Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for treatment of phenylketonuria. PNAS 2008; 105: 20894–20899
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2010 Issue 7-8
Most read in this issue
- Present Opportunities for Treatment of Hyperphenylalaninemia
- Revised Guidelines for Diagnosis, Therapy and Prevention Cow Milk Protein Allergy
- Assessment of Arterial Wall Stiffness by Measurement of Pulse Wave Velocity in Children
- Clinical Symptoms and Laboratory Data in 75 Children with Neonatal Manifestation of Mitochondrial Disease: Proposed Diagnostic Algorithms