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García Restrepo, N., Hernández G., J., Londoño, M. L., & Muriel Ramírez, R. (2018). Deficiencia de fenilalanina hidroxilasa : espectro clínico y estado actual del diagnóstico en Colombia. Biosalud, 17(1), 49–64. https://doi.org/10.17151/biosa.2018.17.1.6
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Las mutaciones del gen PAH generan deficiencia de la enzima fenilalanina hidroxilasa. Su actividad final varía desde una actividad casi nula o indetectable en la fenilcetonuria clásica hasta una actividad residual del 10 al 35% de la normal. Esta alteración corresponde al error innato del metabolismo de los aminoácidos más frecuente, afectando a 1 de cada 10.000 personas. Las diferentes cantidades de fenilalanina en sangre se traducen en un espectro amplio de manifestaciones clínicas que incluyen retraso global del desarrollo, discapacidad intelectual, convulsiones, rasgos autistas y comportamiento agresivo en los casos más graves. El diagnóstico temprano a través de los programas de tamizaje neonatal se considera prioritario pues las intervenciones oportunas evitan el daño del sistema nervioso central. Conclusiones: El diagnóstico en Colombia es tardío, las intervenciones realizadas a partir de ese momento son fútiles pues el deterioro cognitivo es irreparable, por lo tanto es imperativa la realización de pruebas diagnósticas tempranas cuando aún las intervenciones médicas pueden impactar la mejoría clínica del paciente con disminución importante de la morbilidad propia de esta patología, convirtiéndose en una necesidad la ampliación del programa de tamizaje neonatal, el cual estaría amparado bajo la ley colombiana de enfermedades huérfanas.
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2. ENZYME entry 1.14.16.1.
3. Babaoğlu Aydaş S, Şirin S, Aslim B. Biochemical analysis of Centaurea depressa phenylalanine ammonia lyase (PAL) for biotechnological applications in phenylketonuria (PKU). Pharm Biol. 2016;54(12):2838- 2884.
4. Al Hafid N, Christodoulou J. Phenylketonuria: a review of current and future treatments. Transl Pediatr. 2015;4(4):304-17.
5. Flydal MI, Martinez A. Phenylalanine Hydroxylase: Funtion, Structure, and regulation. IUBMB. 2013;64:341-9.
6. Patel D, Kopec J, Fitzpatrick F, McCorvie TJ, Yue WW. Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. Sci Rep. 2016;6:23748. doi: 10.1038/srep23748.
7. OMIM Entry - # 261600 - Phenylketonuria; PKU.
8. Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-200.
9. Cleary M, Trefz F, Muntau AC, Feillet F, van Sprosen FJ, Burlina A, et al. Fluctuations in phenylalanine concentrations in phenylketonuria: A review of possible relationships with outcomes. Mol Genet Metab. 2013;10(4):418-423.
10. White DA, Waisbren S, van Spronsen FJ. Final commentary: A new chapter. Mol Genet Metab. 2010;99:S106-7.
11. Otręba M, Buszman E, Miliński M, Wrześniok D. [Hypomelanoses transmitted from generation to generation]. Postpy Hig Med Dośw Online. 2014;68:1081-1090.
12. Pereda-Torales L, Calcáneo-García JA, Enríquez-Torrecilla R, Badillo-Báez EM, Soler-Huerta E. Identificación de un caso de fenilcetonuria a través del tamizaje neonatal. Bol Méd Hosp Infant México. 2008;65(4):290-296.
13. Vela-Amieva M, Ibarra-González I, Belmont-Martínez L. Tamiz neonatal y fenilcetonuria. Acta Pediátrica México. 2014;33(6):271.
14. Lemes A, Queijo C, Garlo P, Machado M, Queiruga G. Pesquisa neonatal. Arch Pediatría Urug. 2012;83(1):40-44.
15. Borrajo GJ. Panorama epidemiológico de la fenilcetonuria (PKU) en Latinoamérica. Acta Pediatr Mex. 2012;33:279-287.
16. Aldámiz-Echevarría L, Llarena M, Bueno MA, Dalmau J, Vitoria I, Fernández-Marmiesse A, et al. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria. J Hum Genet. 2016;61(8):731-744.
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18. Borrajo GJC. Newborn screening in Latin America at the beginning of the 21st century. J Inherit Metab Dis. 2007;30(4):466-481.
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