Vela-Amieva M, Ibarra-González I, Monroy-Santoyo S, Fernández-Laínez C, Guillén-López S, Belmont-Martínez L, Hernández-Montiel A, González-del Angel A, Ruiz-García M, Sánchez-Pérez MC, Mejía-Navarro J, Iracheta-Gerez ML

Language: Spanish
References: 24
Page: 297-303
PDF size: 273.33 Kb.

ABSTRACT

Hyperphenylalaninemias are a group of autosomal recessive diseases produced in 98% of the cases by impaired activity of phenylalanine hydroxilase (PAH). The phenotype ranges from classic phenylketonuria (OMIM 261600, CIE-10 E090) to mild hyperphenylalaninemia. A high blood level of phenylalanine produces chronic encephalopathy in children, characterized by vomit, refusal to eat, irritability, skin and hair hypopigmentation, eczema, myoclonus, seizures and delay in developmental milestones whose final consequence is usually severe and irreversible mental retardation. For almost 50 years it has been known that early treatment of these conditions attenuates brain damage and can prevent intellectual and motor disabilities. Hyperphenylalaninemia is the most common aminoacid metabolic disorder diagnosed at the Instituto Nacional de Pediatría (INP). This Institute has a long and well documented experience in this disease; it is a referral centre with a multidisciplinary team, advanced technology for the diagnosis and follow-up of patients. The objective of this paper is to show the workshop algorithms for patients suspected of hyperphenylalaninemia seen at the INP, from their first visit at the outpatient clinic to the final diagnosis, in order to provide timely management.

REFERENCES

1. Erlandsen H, Pey A, Gámez A, Pérez B, Desviat L, Aguado C, Koch R, Surendran S, Tyring S, Matalon R, Scriver C, Ugarte M, Martínez A and Stevens R. Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations. PNAS. 2004; 30 (101): 16903-8.

2. Scriver C, Kaufman S. Hyperphenylalaninemia: Phenylalanine hydroxylase deficiency. In Scriver CR, beaudet AL, Sly WS Valle D. eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed New York: Mc Graw Hill; 2001. p. 1667-724.

3. Cornejo V, Raimann E. Errores innatos del metabolismo de los aminoácidos: Hiperfenilalaninemias, en Colombo M, Cornejo V, Raimann E. Errores Innatos en el metabolismo del niño. 1ª edición, Santiago de Chile: 1999. p. 59-65.

4. Blau N, Blaskovics ME. Hyperphenylalaninemia. En: Blau N, Duran M, Blaskovics M (eds): Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases. Chapman and Hall Medical; 1996. p. 65-78.

5. Longo N. Disorders of biopterin metabolism, J Inherit Metab Dis 2009;32(3):333-42.

6. Velázquez A, Bilbao G, González-Trujillo LJ, Hernández D, Pérez-Andrade ME, Vela M, Cicerón I, Loera-Luna A, Cederbaum S and Phoenix B. Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco. Human Genetics 1996;97:99-102.

7. Smith I, Philip L. The hyperphenylalaninemias, En: Fernandes J. Saudubray JM, Van den Berghe G (eds): Inborn Metabolic Diseases, diagnosis and treatment. 3rd edition, Germany: Springer-Verlag; 2000. p. 171-83.

8. Clague A, Thomas A. Neonatal biochemical screening for disease. Clin Chim Acta 2002;315:99.

9. Dale Y, Mackey V, Mushi R, Nyanda A, Maleque M, Ike J. Simultaneous measurement of phenylalanine and tyrosine in phenylketonuric plasma and dried blood by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2003;788(1):1-8.

10. Schwarz EL, Roberts WL, Pasquali M. Analysis of plasma amino acids by HPLC with photodiode array and fluorescence detection. Clinica Chimica Acta 2005;354:83-90.

11. Valedo MT, de Frutos M, Diez-Masa JC. On-capillary derivatization and analysis of amino acids in human plasma by capillary electrophoresis with laser-induced fluorescence detection: Application to diagnosis of aminoacidopathies. Electrophoresis 2006;27:3101-7.

12. Perez B, Desviat LR, De Lucca M, Schmidt B., Loghin-Grosso N, Giugliani R, Pires RF, Ugarte M. Mutation analysis of phenylketonuria in South Brazil. Human Mutation 1996;8:262-4.

13. Santana da Silva LC, Santos Carvalho T, Britto da Silva F, Morari L, Aguirres Fachel A, Pires R, Farret Refosco L, Desnick RJ, Giugliani R, Saraiva Pereira ML. Molecular characterization of phenylketonuria in South Brazil Molecular Genetics and Metabolism 2003;79:17-24.

14. www.pahdb.mcgill.ca

15. Tighe O, Dunican D, O´Neill C., Bertorelle G, Beattie D, Graham C, et al. Genetic Diversity Within the R408W Phenylketonuria Mutation Lineages in Europe. Human Mutation 2003;21:387-93.

16. Vallian S, Barahimi E, Moeini H. Phenylketonuria in Iranian population: a study in institutions for mentally retarded in Isfahan. Mutation Research 2003;526:45-52.

17. Camfield CS, Joseph M, Hurley T, Campbell K, Sanderson S, Camfield PR. Optimal management of phenylketonuria: a centralized expert tea mis more successful than a decentralized model of care. J Pediatr 2004;145:53-7.

18. Draft recommendations for the development of strategic plan for rare diseases including methodological guidance. 28 October, 2009. Final recommendations available on the EUROPLAN website, www.europlanproject.eu;

19. Godard B, Kääriäinen H, Kristoffersson U, Tranebjaerg L , Coviello D, Aymé S. Provision of genetic services in Europe: current practices and issues. Eur J Human Genet 2003;11(Suppl 2):S13–S48.

20. van Spronsen FJ, Ahring KK, Gizewska M. PKU-what is daily practice in various centres in Europe? Data from a questionnaire by the scientific advisory committee of the European Society of Phenylketonuria and Allied Disorders, J Inherit Metab Dis 2009;32:58–64.

21. Blau N, Belanger-Quintana A, Demirkol M, Feillet F, Giovannini M, MacDonald A, Trefz FK, van Spronsen FJ. Management of phenylketonuria in Europe: survey results from 19 countries, Mol Genet Metab 2009;96:158–63.

22. Penchaszadeh VB, Christianson AL, Giugliani R, Boulyjenkov V, Katz M. Services for the prevention and management of genetic disorders and birth defects in developing countries. Comm Genet 1999;2:196–201.

23. National Institutes of Health Consensus Development Panel; National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16-18, 2000. Pediatrics 2001;108: 972–82.

24. Waisbren SE, Noel K, Fahrbach K, Cella C, Frame D, Dorenbaum A, Levy H. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab 2007;92(1-2):63-70.