Abstract
The present study aimed to retrospectively evaluate a cohort of patients diagnosed with phenylketonuria, screened by the heel prick test and confirmed by serum phenylalanine measurement by the neonatal screening service in the state of Mato Grosso do Sul, IPED/Apae (SRTN –MS IPED/Apae), the connection between therapeutic adherence and the quantification of breastfeeding and the achievement of age-appropriate neuropsychomotor development. Methods: Retrospective cohort study involved patients treated from July to December 2022, of the 20 patients seen during this period, 5 were excluded from the analysis of data on control of serum phenylalanine while breastfeeding due to lack of data regarding treatment and levels of phenylketonuria in the first year of life, once, who lived in other states and were monitored in other services. Of the patients who participated, clinical and biochemical data, as well as demographic, social and treatment data, were analyzed from medical records. Results: In this group there was 1 case of consanguinity. 66.6% of patients were male. Most patients were diagnosed with classic phenylketonuria (46.6%), followed by 40% with mild phenylketonuria and only 13.3% with a diagnosis of other forms of phenylketonuria. The patients belonged to socioeconomic classes B2, C1, C2, D-E. It was not possible to establish a correlation between the socioeconomic class of patients and better control of the disease. Only two patients presented a delay in neuropsychomotor development, one with non-phenylketonuric hyperphenylalanine and the other with benign hyperphenylaninemia, in both cases the delay is not correlated with hyperphenylaninemia. Conclusion: Phenylketonuria has a good prognosis when diagnosed early and adequate therapy and monitoring are instituted. There is no consensus regarding the suspension of breastfeeding. Studies stating an age/serum phenylalanine dosage that indicates the need to discontinue breastfeeding are encouraged.
References
Agency for Healthcare Research and Quality. Comparative Effectiveness of Treatment for Phenylketonuria (PKU). Comparative Effectiveness Review No. 56. Prepared by the Vanderbilt Evidence-Based Practice Center under Contract No. 290-2007-10065-I. AHRQ Publication No. 12-EHC035-EF. 2011. http://www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Anikster, Y., Haack, T. B., Vilboux, T., Pode-Shakked, B., Thöny, B., Shen, N., Guarani, V., Meissner, T., Mayatepek, E., Trefz, F. K., Marek-Yagel, D., Martinez, A., Huttlin, E. L., Paulo, J. A., Berutti, R., Benoist, J. F., Imbard, A., Dorboz, I., Heimer, G., Landau, Y., … Schiff, M. (2017). Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. American journal of human genetics, 100(2), 257–266. https://doi.org/10.1016/j.ajhg.2017.01.002
Banta-Wright, S. A., Press, N., Knafl, K. A., Steiner, R. D., & Houck, G. M. (2014). Breastfeeding infants with phenylketonuria in the United States and Canada. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, 9(3), 142–148. https://doi.org/10.1089/bfm.2013.0092
Blau, N., van Spronsen, F. J., & Levy, H. L. (2010). Phenylketonuria. Lancet (London, England), 376(9750), 1417–1427. https://doi.org/10.1016/S0140-6736(10)60961-0
Burton, B. K., Adams, D. J., Grange, D. K., Malone, J. I., Jurecki, E., Bausell, H., Marra, K. D., Sprietsma, L., & Swan, K. T. (2011). Tetrahydrobiopterin therapy for phenylketonuria in infants and young children. The Journal of pediatrics, 158(3), 410–415. https://doi.org/10.1016/j.jpeds.2010.08.016
Camp, K. M., Parisi, M. A., Acosta, P. B., Berry, G. T., Bilder, D. A., Blau, N., Bodamer, O. A., Brosco, J. P., Brown, C. S., Burlina, A. B., Burton, B. K., Chang, C. S., Coates, P. M., Cunningham, A. C., Dobrowolski, S. F., Ferguson, J. H., Franklin, T. D., Frazier, D. M., Grange, D. K., Greene, C. L., … Young, J. M. (2014). Phenylketonuria Scientific Review Conference: state of the science and future research needs. Molecular genetics and metabolism, 112(2), 87–122. https://doi.org/10.1016/j.ymgme.2014.02.013
Fiege, B., & Blau, N. (2007). Assessment of tetrahydrobiopterin (BH4) responsiveness in phenylketonuria. The Journal of pediatrics, 150(6), 627–630. https://doi.org/10.1016/j.jpeds.2007.02.017
Gizewska, M., Cabalska, B., Cyrytowski, L., Nowacki, P., Zekanowski, C., Walczak, M., Jóźwiak, I., & Koziarska, D. (2003). Diferentes apresentações de fenilcetonúria detectada tardiamente em dois irmãos com o mesmo genótipo R408W/R111X no gene HAP. Jornal de pesquisa de deficiência intelectual: JIDR, 47(Pt 2), 146–152. https://doi.org/10.1046/j.1365-2788.2003.00449.x
Hillert, A., Anikster, Y., Belanger-Quintana, A., Burlina, A., Burton, B. K., Carducci, C., Chiesa, A. E., Christodoulou, J., Đorđević, M., Desviat, L. R., Eliyahu, A., Evers, R. A. F., Fajkusova, L., Feillet, F., Bonfim-Freitas, P. E., Giżewska, M., Gundorova, P., Karall, D., Kneller, K., Kutsev, S. I., … Blau, N. (2020). The Genetic Landscape and Epidemiology of Phenylketonuria. American journal of human genetics, 107(2), 234–250. https://doi.org/10.1016/j.ajhg.2020.06.006
Hörnell, A., Lagström, H., Lande, B., & Thorsdottir, I. (2013). Breastfeeding, introduction of other foods and effects on health: a systematic literature review for the 5th Nordic Nutrition Recommendations. Food & nutrition research, 57, 10.3402/fnr.v57i0.20823. https://doi.org/10.3402/fnr.v57i0.20823
Jahja, R., van Spronsen, F. J., de Sonneville, L. M. J., van der Meere, J. J., Bosch, A. M., Hollak, C. E. M., Rubio-Gozalbo, M. E., Brouwers, M. C. G. J., Hofstede, F. C., de Vries, M. C., Janssen, M. C. H., van der Ploeg, A. T., Langendonk, J. G., & Huijbregts, S. C. J. (2016). Social-cognitive functioning and social skills in patients with early treated phenylketonuria: a PKU-COBESO study. Journal of inherited metabolic disease, 39(3), 355–362. https://doi.org/10.1007/s10545-016-9918-0
Kalvala, J., Chong, L., Chadborn, N., & Ojha, S. (2023). Breast feeding in infants diagnosed with phenylketonuria (PKU): a scoping review. BMJ paediatrics open, 7(1), e002066. https://doi.org/10.1136/bmjpo-2023-002066
Kanufre, V. C., Starling, A. L., Leão, E., Aguiar, M. J., Santos, J. S., Soares, R. D., & Silveira, A. M. (2007). Breastfeeding in the treatment of children with phenylketonuria. Jornal de pediatria, 83(5), 447–452. https://doi.org/10.2223/JPED.1672
Kose, E., Aksoy, B., Kuyum, P., Tuncer, N., Arslan, N., & Ozturk, Y. (2018). The Effects of Breastfeeding in Infants With Phenylketonuria. Journal of pediatric nursing, 38, 27–32. https://doi.org/10.1016/j.pedn.2017.10.009
Lamônica, D. A., Stump, M. V., Pedro, K. P., Rolim-Liporacci, M. C., Caldeira, A. C., Anastácio-Pessan, F.daL., & Gejão, M. G. (2012). Breastfeeding follow-up in the treatment of children with phenylketonuria. Jornal da Sociedade Brasileira de Fonoaudiologia, 24(4), 386–389. https://doi.org/10.1590/s2179-64912012000400016
Monteiro, G. M., Campos, E. V., Santos Neto, A. T., Pontes, E. R. J. C, Ivo, Maria Lucia, Marcheti, M. A., Cardoso, A. I. Q. & Giuliani, L. R. (2019). Effectiveness of phenylketonuria diagnosis in the neonatal treatment reference service. International Journal for Innovation Education and Research, v. 7, p. 374-384.
Qi, Y., Mould, D. R., Zhou, H., Merilainen, M., & Musson, D. G. (2015). A prospective population pharmacokinetic analysis of sapropterin dihydrochloride in infants and young children with phenylketonuria. Clinical pharmacokinetics, 54(2), 195–207. https://doi.org/10.1007/s40262-014-0196-4
Riva, E., Agostoni, C., Biasucci, G., Trojan, S., Luotti, D., Fiori, L., & Giovannini, M. (1996). Early breastfeeding is linked to higher intelligence quotient scores in dietary treated phenylketonuric children. Acta paediatrica (Oslo, Norway : 1992), 85(1), 56–58. https://doi.org/10.1111/j.1651-2227.1996.tb13890.x
Rollins, N. C., Bhandari, N., Hajeebhoy, N., Horton, S., Lutter, C. K., Martines, J. C., Piwoz, E. G., Richter, L. M., Victora, C. G., & Lancet Breastfeeding Series Group (2016). Why invest, and what it will take to improve breastfeeding practices?. Lancet (London, England), 387(10017), 491–504. https://doi.org/10.1016/S0140-6736(15)01044-2
Scriver C. R. (2007). The PAH gene, phenylketonuria, and a paradigm shift. Human mutation, 28(9), 831–845. https://doi.org/10.1002/humu.20526
Smith, I., Beasley, M. G., & Ades, A. E. (1990). Intelligence and quality of dietary treatment in phenylketonuria. Archives of disease in childhood, 65(5), 472–478. https://doi.org/10.1136/adc.65.5.472
ten Hoedt, A. E., de Sonneville, L. M., Francois, B., ter Horst, N. M., Janssen, M. C., Rubio-Gozalbo, M. E., Wijburg, F. A., Hollak, C. E., & Bosch, A. M. (2011). High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial. Journal of inherited metabolic disease, 34(1), 165–171. https://doi.org/10.1007/s10545-010-9253-9
van Rijn, M., Bekhof, J., Dijkstra, T., Smit, P. G., Moddermam, P., & van Spronsen, F. J. (2003). A different approach to breast-feeding of the infant with phenylketonuria. European journal of pediatrics, 162(5), 323–326. https://doi.org/10.1007/s00431-003-1182-2
van Spronsen, F. J., Blau, N., Harding, C., Burlina, A., Longo, N., & Bosch, A. M. (2021). Fenilketonúria. Revisões da natureza. Primers de doenças, 7(1), 36. https://doi.org/10.1038/s41572-021-00267-0
van Wegberg, A. M. J., MacDonald, A., Ahring, K., Bélanger-Quintana, A., Blau, N., Bosch, A. M., Burlina, A., Campistol, J., Feillet, F., Giżewska, M., Huijbregts, S. C., Kearney, S., Leuzzi, V., Maillot, F., Muntau, A. C., van Rijn, M., Trefz, F., Walter, J. H., & van Spronsen, F. J. (2017). As diretrizes europeias completas sobre fenilcetonúria: diagnóstico e tratamento. Jornal Orphanet de doenças raras, 12(1), 162. https://doi.org/10.1186/s13023-017-0685-2
Zhang, Z., Adelman, A. S., Rai, D., Boettcher, J., & Lőnnerdal, B. (2013). Amino acid profiles in term and preterm human milk through lactation: a systematic review. Nutrients, 5(12), 4800–4821. https://doi.org/10.3390/nu5124800

This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2024 Edson Rodrigues Arimura , Liane de Rosso Giuliani , Poliana Lemes Araújo , Mayaha Bárbara Oliveira do Nascimento Machado , Têmis Maria Félix