Scoping review del manejo nutricional en tirosinemia tipo II

Esta revisión de alcance investigó las estrategias nutricionales para el manejo de la tirosinemia tipo II, un trastorno genético autosómico recesivo causado por mutaciones en el gen que codifica la enzima tirosina aminotransferasa (TAT), cuya deficiencia provoca una acumulación de tirosina y sus met...

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Autores:
Gómez Gómez, Laura Johana
Tipo de recurso:
https://purl.org/coar/resource_type/c_7a1f
Fecha de publicación:
2025
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
spa
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/15618
Acceso en línea:
https://hdl.handle.net/20.500.12495/15618
Palabra clave:
Tirosinemia tipo 2
TAT
Sindrome de Richner-hanhart
Dieta
Manejo nutricional
Epidemiología
Tyrosinemia type II
TAT
Richner-Hanhart syndrome
Nutritional management
Rare diseases
Epidemiology
WB 115
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License
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dc.title.none.fl_str_mv Scoping review del manejo nutricional en tirosinemia tipo II
dc.title.translated.none.fl_str_mv Nutritional management of Tyrosinemia Type II: A scoping review of clinical evidence and future directions (2017–2025)
title Scoping review del manejo nutricional en tirosinemia tipo II
spellingShingle Scoping review del manejo nutricional en tirosinemia tipo II
Tirosinemia tipo 2
TAT
Sindrome de Richner-hanhart
Dieta
Manejo nutricional
Epidemiología
Tyrosinemia type II
TAT
Richner-Hanhart syndrome
Nutritional management
Rare diseases
Epidemiology
WB 115
title_short Scoping review del manejo nutricional en tirosinemia tipo II
title_full Scoping review del manejo nutricional en tirosinemia tipo II
title_fullStr Scoping review del manejo nutricional en tirosinemia tipo II
title_full_unstemmed Scoping review del manejo nutricional en tirosinemia tipo II
title_sort Scoping review del manejo nutricional en tirosinemia tipo II
dc.creator.fl_str_mv Gómez Gómez, Laura Johana
dc.contributor.advisor.none.fl_str_mv Amaya Rodriguez, Kelly
Gónzalez Devia, Deyanira
dc.contributor.author.none.fl_str_mv Gómez Gómez, Laura Johana
dc.contributor.orcid.none.fl_str_mv Gómez Gómez, Laura Johana [0000-0002-9957-6792]
Gónzalez Devia, Deyanira [0000-0003-3378-2312]
dc.subject.none.fl_str_mv Tirosinemia tipo 2
TAT
Sindrome de Richner-hanhart
Dieta
Manejo nutricional
Epidemiología
topic Tirosinemia tipo 2
TAT
Sindrome de Richner-hanhart
Dieta
Manejo nutricional
Epidemiología
Tyrosinemia type II
TAT
Richner-Hanhart syndrome
Nutritional management
Rare diseases
Epidemiology
WB 115
dc.subject.keywords.none.fl_str_mv Tyrosinemia type II
TAT
Richner-Hanhart syndrome
Nutritional management
Rare diseases
Epidemiology
dc.subject.nlm.none.fl_str_mv WB 115
description Esta revisión de alcance investigó las estrategias nutricionales para el manejo de la tirosinemia tipo II, un trastorno genético autosómico recesivo causado por mutaciones en el gen que codifica la enzima tirosina aminotransferasa (TAT), cuya deficiencia provoca una acumulación de tirosina y sus metabolitos. Las manifestaciones clínicas incluyeron alteraciones neurológicas, cutáneas y visuales. El manejo de la enfermedad es complejo y depende en gran medida de una dieta con restricción de por vida de tirosina y fenilalanina, baja en proteínas, combinada con suplementos de aminoácidos apropiados para la edad. Un control dietético tardío puede estar relacionado con ciertos trastornos del lenguaje y la poca adherencia, con recurrencia de los síntomas. Por ello, el objetivo fue identificar, explorar y sintetizar la evidencia disponible con relación al manejo nutricional de esta patología, dada la escasa literatura y su impacto sistémico. Se recopilaron 38 artículos publicados en los últimos ocho años, seleccionados mediante estrategias de búsqueda en bases de datos científicas, empleando términos MESH y siguiendo las guías PRISMA-ScR 2018 y JBI 2024. Se analizaron dietas restrictivas en tirosina y fenilalanina, suplementación con aminoácidos y su relación con la prevención de complicaciones. Los resultados confirmaron que la restricción dietética fue fundamental para reducir los síntomas, prevenir complicaciones y mejorar la calidad de vida de los pacientes, aunque se requieren más estudios que evalúen adherencia y suplementación a largo plazo. Palabras clave: Tirosinemia tipo 2, TAT, Sindrome de Richner-hanhart, Dieta, Manejo nutricional
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-07-31T21:48:18Z
dc.date.available.none.fl_str_mv 2025-07-31T21:48:18Z
dc.date.issued.none.fl_str_mv 2025-06
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.local.spa.fl_str_mv Tesis/Trabajo de grado - Monografía - Especialización
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dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
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dc.relation.references.none.fl_str_mv 1. den Hollander B, Hoytema van Konijnenburg EMM, Hewitson B, van der Meijden JC, Balfoort BM, Winter B, et al. The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat! J Inherit Metab Dis. 2025;48(1):e12835. doi:10.1002/jimd.12835.
2. Piñar-Gutiérrez A, Dios Fuentes E, Benítez-Ávila R, de Ana-Lobato L, Bueno-Delgado MDA, Soto-Moreno A, et al. Maternal-fetal outcomes of pregnancies in women treated at an inborn errors of metabolism unit. Endocrinol Diabetes Nutr. 2023;70(2):98–106. doi:10.1016/j.endien.2022.09.006.
3. Tiivoja E, Reinson K, Muru K, Rähn K, Muhu K, Mauring L, et al. The prevalence of inherited metabolic disorders in Estonian population over 30 years: A significant increase during study period. JIMD Rep. 2022;63(6):604–13. doi:10.1002/jmd2.12325.
4. Borrajo GJC. Newborn screening in Latin America: A brief overview of the state of the art. Am J Med Genet C Semin Med Genet. 2021;187(3):322–8. doi:10.1002/ajmg.c.31899.
5. Echeverri OY, Guevara JM, Espejo-Mojica ÁJ, Ardila A, Pulido N, Reyes M, et al. Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years' experience from a reference center. Orphanet J Rare Dis. 2018;13(1):141. doi:10.1186/s13023-018-0879-2.
6. Orphanet. Tyrosinemia type 2 [Internet]. Paris: Orphanet; 2023 [cited 2024 Dec 18]. Available from: https://www.orpha.net/en/disease/detail/28378
7. Beyzaei Z, Nabavizadeh S, Karimzadeh S, Geramizadeh B. The mutation spectrum and ethnic distribution of non-hepatorenal tyrosinemia (types II, III). Orphanet J Rare Dis. 2022;17(1):424. https://doi.org/10.1186/s13023-022-02579-0
8. Bayzaei Z, Dehghani SM, Geramizadeh B. Tyrosinemia Type II. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025 [updated 2024 Oct 24; cited 2024 Dic 06]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK608431/
9. Peña-Quintana L, Scherer G, Curbelo-Estévez ML, et al. Tyrosinemia Type II: mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation. Clin Genet. 2017;92(3):306–17. doi:10.1111/cge.13003
10. van Spronsen FJ, Burlina A, Dionisi Vici C. Tyrosine metabolism. In: Blau N, Dionisi Vici C, Ferreira CR, Vianey-Saban C, van Karnebeek CDM, editors. Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Cham: Springer; 2022. p. 1–20. doi:10.1007/978-3-030-67727-5_21.
11. Bose S, Mandal S, Khan R, Maji HS, Ashique S. Current landscape on development of phenylalanine and toxicity of its metabolites - a review. Curr Drug Saf. 2024;19(2):208-217. doi:10.2174/1574886318666230331112800.
12. Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H. Aminoacidopathies: prevalence, etiology, screening, and treatment options. Biochem Genet. 2018;56(1-2):7-21. doi:10.1007/s10528-017-9825-6.
13. Meléndrez-Vásquez D, Ossa Trujillo RH, Zarante-Bahamón AM, Rojas JA, Tamayo M. Palmo-plantar keratoderma secondary to tyrosinemia type II. Piel. 2024. doi:10.1016/j.piel.2024.04.005.
14. Gliagias V, Denisova K, Kang JJ. A child with dendritiform eye lesions and developmental delay. Am J Ophthalmol Case Rep. 2022;28:101701. doi:10.1016/j.ajoc.2022.101701.
15. Locatelli F, Puzenat E, Arnoux JB, Blanc D, Aubin F. Richner-Hanhart syndrome (tyrosinemia type II). Cutis. 2017;100(6):E20–2.
16. Miranda BA, Rocha ACH, Arantes RR, Kanufre VC, Silva SC, Vasconcelos-Santos DV. Bilateral recurrent pseudodendritic keratopathy as the initial manifestation of tyrosinemia type II. Ophthalmic Genet. 2022;43(2):282–4. doi:10.1080/13816810.2022.2034168
17. Daly A, Adam S, Allen H, Ash J, Dale C, Dixon M, et al. UK dietary practices for tyrosinaemias: time for change. Nutrients. 2022;14(24):5202. doi:10.3390/nu14245202
18. Delsoglio M, Capener R, MacDonald A, Daly A, Ashmore C, Donald S, et al. Evaluation of a new 'mix-in' style glycomacropeptide-based protein substitute for food and drinks in patients with phenylketonuria and tyrosinemia. Nutrients. 2023;15(16):3598. doi:10.3390/nu15163598
19. Peacock DJSJ, Ferreira CR, Horvath G, Hoffmann GF, Blau N, Ebrahimi-Fakhari D. Clinical and biochemical footprints of inherited metabolic diseases: Ia. Movement disorders, updated. Mol Genet Metab. 2025;145(1):109084. doi:10.1016/j.ymgme.2025.109084
20. Carvalho-Silva M, Gomes LM, Scaini G, Rebelo J, Damiani AP, Pereira M, et al. Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II. Metab Brain Dis. 2017;32(4):1043–50.
21. Antonini R, Scaini G, Michels M, Matias MBD, Schuck PF, Ferreira GC, et al. Effects of omega-3 fatty acids supplementation on inflammatory parameters after chronic administration of L-tyrosine. Metab Brain Dis. 2020;35(2):295–303.
22. Thibault LP, Mitchell GA, Parisien B, Hamel P, Blanchard AC. An infant with bilateral keratitis: From infectious to genetic diagnosis. Am J Case Rep. 2022;23:e937967.
23. Teodorak BP, Scaini G, Carvalho-Silva M, Gomes LM, Teixeira LJ, Rebelo J, De Prá SD, Zeni N, Schuck PF, Ferreira GC, Streck EL. Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L-tyrosine. Metab Brain Dis. 2017;32(2):557–64.
24. Carvalho-Silva M, Gomes LM, Gomes ML, Ferreira BK, Schuck PF, Ferreira GC, Dal-Pizzol F, de Oliveira J, Scaini G, Streck EL. Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats. Metab Brain Dis. 2019;34(4):1207–1219. doi:10.1007/s11011-019-00411-6.
25. Gomes LM, Scaini G, Carvalho-Silva M, Gomes ML, Malgarin F, Kist LW, Bogo MR, Rico EP, Zugno AI, Deroza PFP, Réus GZ, de Moura AB, Quevedo J, Ferreira GC, Schuck PF, Streck EL. Antioxidants reverse the changes in the cholinergic system caused by L-tyrosine administration in rats. Neurotox Res. 2018;34(4):769–780. doi:10.1007/s12640-018-9866-6.
26. Manta-Vogli PD, Schulpis KH, Dotsikas Y, Loukas YL. Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs). J Pediatr Endocrinol Metab. 2020;33(1):5–20. doi:10.1515/jpem-2019-0048.
27. Saudubray JM, Baumgartner MR, García-Cazorla Á, Walter J. Disorders of Tyrosine Metabolism. In: Inborn Metabolic Diseases: Diagnosis and Treatment [Internet]. Berlin: Springer; 2022 [cited 2025 May 25]. Available from: https://research.ebsco.com/linkprocessor/plink?id=8428acb6-e645-3321-bea2-c53ebfc81a4e.
28. Martin GC, de Lonlay P, Chapron T, Cochereau I, Caputo G, Gabison E. Bilateral dendriform ulcer leading to an early diagnosis of tyrosinemia type 2. J AAPOS. 2020;24(2):120–2. doi:10.1016/j.jaapos.2019.12.007.
29. Mohite AA, Abbott J. Photophobia accompanied by painful plantar punctate hyperkeratotic patches: Tyrosinemia type 2. Indian J Ophthalmol. 2018 Mar;66(3):449. doi:10.4103/ijo.ijo_820_17. PMID: 29480263; PMCID: PMC5859607.
30. Ghalamkarpour F, Niknezhad N, Niknejad N. Familial Richner-Hanhart syndrome: Report of a sibling with incomplete presentation. Dermatol Ther. 2020;33(6):e14072. doi:10.1111/dth.14072.
31. da Silva ISF, Sopa I, Gomes D, Peixoto L, Oliveira A. From skin lesions to tyrosinemia type II diagnosis. J Inherit Metab Dis. 2024;47(5):1107–1108. doi:10.1002/jimd.12720.
32. Streck EL, De Prá SDT, Ferro PR, Carvalho-Silva M, Gomes LM, Agostini JF, Damiani A, Andrade VM, Schuck PF, Ferreira GC, Scaini G. Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II. Mol Cell Biochem. 2017;435(1-2):207–214. doi:10.1007/s11010-017-3070-5.
33. Hannah-Shmouni F, MacNeil L, Lara-Corrales I, Pope E, Kannu P, Sondheimer N. Whole-exome sequencing identifies a homozygous pathogenic variant in TAT in a girl with palmoplantar keratoderma. Mol Genet Metab Rep. 2019;21:100534. doi:10.1016/j.ymgmr.2019.100534.
34. Soares DC, Stroparo MN, Lian YC, Takakura CY, Wolf S, Betz R, Kim CA. Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome. J Inherit Metab Dis. 2017;40(3):461–462. doi:10.1007/s10545-016-9996-z.
35. Chakrapani A, Gissen P, McKiernan P. Inborn Metabolic Diseases: Diagnosis and Treatment. Chapter 17: Disorders of Tyrosine Metabolism [Internet]. Berlin: Springer; 2022 [cited 2025 May 25]. Available from: http://ndl.ethernet.edu.et/bitstream/123456789/55539/1/50.pdf
36. Rupec RA. Braun-Falco's Dermatology. Chapter 91: Disorders of Purine, Sphingolipid, and Amino Acid Metabolism [Internet]. Berlin, Heidelberg: Springer; 2022 [cited 2025 May 25]. Available from: https://research.ebsco.com/linkprocessor/plink?id=f7c5abb8-69b4-392b-b182-fa91c23dfa41
37. Al Jasmi F, Galadari H, Clayton PT, Footitt EJ. Metabolic disorders and the skin. In: Hoeger P, Kinsler V, Yan A, Harper J, Oranje A, Bodemer C, Larralde M, Luk D, Mendiratta V, Purvis D, editors. Harper's Textbook of Pediatric Dermatology [Internet]. Chichester, UK: Wiley-Blackwell; 2019 [cited 2025 May 25]. Available from: https://doi.org/10.1002/9781119142812.ch152
38. Khochtali S, Daldoul N, Zina S, Kadri A, Ben Yahia S, Khairallah M. Atteinte cornéenne liée à une tyrosinémie de type II mimant une kératite herpétique: à propos d’un cas chez un adulte. J Fr Ophtalmol. 2018;41(7):e315–e318. https://doi.org/10.1016/j.jfo.2017.09.028
39. Alsharhan H, Ficicioglu C. Disorders of phenylalanine and tyrosine metabolism. Transl Sci Rare Dis. 2020;5(1–2):3–58. doi:10.3233/TRD-200049
40. Aliu E, Kanungo S, Arnold G. Amino acid disorders. Ann Transl Med. 2018;6(24):471. doi:10.21037/atm.2018.12.12
41. Marek S, Linaburg T, Nguyen BJ. Inborn errors of metabolism and their corneal manifestations. Adv Ophthalmol Optom. 2023;8(1):329–41. doi:10.1016/j.yaoo.2023.02.015.
42. Jones P, Patel K, Rakheja D. Disorder: Tyrosinemia types 2 and 3. In: Jones P, Patel K, Rakheja D, editors. A Quick Guide to Metabolic Disease Testing Interpretation. 2nd ed. Academic Press; 2020. p. 127–30. doi:10.1016/B978-0-12-816926-1.00024-9.
43. Rosenberg RN, Pascual JM. Inborn errors of amino acid metabolism. In: Rosenberg RN, Pascual JM, editors. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. 7th ed. Academic Press; 2025. p. 761–77. doi:10.1016/B978-0-443-19041-4.00046-7.
44. Chirita-Emandi A. Screening for inborn errors of metabolism. In: DE Caterina R, Martinez JA, Kohlmeier M, editors. Principles of Nutrigenetics and Nutrigenomics. Academic Press; 2020. p. 153–8. doi:10.1016/B978-0-12-804572-5.00019-7.
45. van Karnebeek CDM, Berry-Kravis E, Gropman A. Treatment of neurodevelopmental disorders. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, Pearl PL, Shevell MI, editors. Swaiman's Pediatric Neurology. 6th ed. Elsevier; 2017. p. 478–88. doi:10.1016/B978-0-323-37101-8.00059-X.
46. Tseng LA, Sowerbutt C, Lee JJY, van Karnebeek CDM. P4 medicine for epilepsy and intellectual disability: nutritional therapy for inherited metabolic disease. Emerg Top Life Sci. 2019;3(1):75–95. doi:10.1042/ETLS20180180.
47. Dalili S, Talea A, Aghajany-Nasab M, Miandoab NAA, Koohmanaee S, Hakemzadeh ST, Medghalchi N. Clinical features and laboratory diagnosis of aminoacidopathies: a narrative review. Evaluation. 2023;1:3.
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spelling Amaya Rodriguez, KellyGónzalez Devia, DeyaniraGómez Gómez, Laura JohanaGómez Gómez, Laura Johana [0000-0002-9957-6792]Gónzalez Devia, Deyanira [0000-0003-3378-2312]2025-07-31T21:48:18Z2025-07-31T21:48:18Z2025-06https://hdl.handle.net/20.500.12495/15618instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coEsta revisión de alcance investigó las estrategias nutricionales para el manejo de la tirosinemia tipo II, un trastorno genético autosómico recesivo causado por mutaciones en el gen que codifica la enzima tirosina aminotransferasa (TAT), cuya deficiencia provoca una acumulación de tirosina y sus metabolitos. Las manifestaciones clínicas incluyeron alteraciones neurológicas, cutáneas y visuales. El manejo de la enfermedad es complejo y depende en gran medida de una dieta con restricción de por vida de tirosina y fenilalanina, baja en proteínas, combinada con suplementos de aminoácidos apropiados para la edad. Un control dietético tardío puede estar relacionado con ciertos trastornos del lenguaje y la poca adherencia, con recurrencia de los síntomas. Por ello, el objetivo fue identificar, explorar y sintetizar la evidencia disponible con relación al manejo nutricional de esta patología, dada la escasa literatura y su impacto sistémico. Se recopilaron 38 artículos publicados en los últimos ocho años, seleccionados mediante estrategias de búsqueda en bases de datos científicas, empleando términos MESH y siguiendo las guías PRISMA-ScR 2018 y JBI 2024. Se analizaron dietas restrictivas en tirosina y fenilalanina, suplementación con aminoácidos y su relación con la prevención de complicaciones. Los resultados confirmaron que la restricción dietética fue fundamental para reducir los síntomas, prevenir complicaciones y mejorar la calidad de vida de los pacientes, aunque se requieren más estudios que evalúen adherencia y suplementación a largo plazo. Palabras clave: Tirosinemia tipo 2, TAT, Sindrome de Richner-hanhart, Dieta, Manejo nutricionalUniversidad El BosqueHospital Universitario Fundación Santa Fé De BogotáEspecialista en Medicina InternaEspecializaciónPurpose: Tyrosinemia type II (HTII) is an inborn error of tyrosine metabolism characterized by cutaneous, ophthalmologic, and neurological manifestations. Its treatment relies primarily on nutritional intervention through the restriction of tyrosine and phenylalanine. However, available evidence on dietary guidelines remains scarce and poorly contextualized. This scoping review aimed to identify nutritional strategies used in HTII over the past eight years, highlight critical gaps in clinical-nutritional management, and describe the epidemiological situation in Colombia. In addition, a nutritional table adapted to the local dietary diversity is proposed as an innovative therapeutic support tool. Methods: A scoping review was conducted following the PRISMA-ScR 2018 guidelines and the Joanna Briggs Institute (JBI) 2024 methodology. International scientific databases were searched to identify studies published between 2017 and 2025 addressing the nutritional management of HTII. Additionally, official reports from the Colombian National Institute of Health and the Ministry of Health were reviewed to characterize the national epidemiological landscape. Results: Among 38 included studies, 76% mentioned dietary restriction of tyrosine and phenylalanine, and 34% referred to overall protein restriction. Nutritional supplementation was reported as follows: amino acids (15%), vitamins, minerals, and omega-3 fatty acids (13%), antioxidants such as N-acetylcysteine and deferoxamine (10%), prescribed formulas (7%), and protein substitutes (2%) (Table 1). A high heterogeneity was observed in target tyrosine levels (serum and urine), monitoring frequency, and criteria for food inclusion based on protein or amino acid content. In response, a nutritional table (Table 2) was developed to classify foods according to protein, tyrosine, and phenylalanine content, using international databases and locally adapted values to support clinical decision-making and improve treatment adherence. Regarding epidemiological findings, only one HTII case was reported in the Sivigila surveillance system between 2017 and February 2025 (Table 3), while the Ministry of Health reported two cases (Table 4). Underreporting and incomplete data on age, location, and year of diagnosis limit public health planning and hinder international comparability. Conclusions: There is a critical gap in the standardization of nutritional treatment for HTII. The available evidence is limited and lacks regional dietary adaptations. This review proposes a practical and contextualized nutritional table that may assist healthcare professionals and patients, improve adherence, prevent systemic complications, and serve as a foundation for future national guidelines and clinical studies. Strengthening epidemiological surveillance is equally essential to ensure a comprehensive approach to this potentially treatable condition.application/pdfTirosinemia tipo 2TATSindrome de Richner-hanhartDietaManejo nutricionalEpidemiologíaTyrosinemia type IITATRichner-Hanhart syndromeNutritional managementRare diseasesEpidemiologyWB 115Scoping review del manejo nutricional en tirosinemia tipo IINutritional management of Tyrosinemia Type II: A scoping review of clinical evidence and future directions (2017–2025)Especialización en Medicina InternaUniversidad El BosqueFacultad de MedicinaTesis/Trabajo de grado - Monografía - Especializaciónhttps://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesishttps://purl.org/coar/version/c_ab4af688f83e57aa1. den Hollander B, Hoytema van Konijnenburg EMM, Hewitson B, van der Meijden JC, Balfoort BM, Winter B, et al. The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat! J Inherit Metab Dis. 2025;48(1):e12835. doi:10.1002/jimd.12835.2. Piñar-Gutiérrez A, Dios Fuentes E, Benítez-Ávila R, de Ana-Lobato L, Bueno-Delgado MDA, Soto-Moreno A, et al. Maternal-fetal outcomes of pregnancies in women treated at an inborn errors of metabolism unit. Endocrinol Diabetes Nutr. 2023;70(2):98–106. doi:10.1016/j.endien.2022.09.006.3. Tiivoja E, Reinson K, Muru K, Rähn K, Muhu K, Mauring L, et al. The prevalence of inherited metabolic disorders in Estonian population over 30 years: A significant increase during study period. JIMD Rep. 2022;63(6):604–13. doi:10.1002/jmd2.12325.4. Borrajo GJC. Newborn screening in Latin America: A brief overview of the state of the art. Am J Med Genet C Semin Med Genet. 2021;187(3):322–8. doi:10.1002/ajmg.c.31899.5. Echeverri OY, Guevara JM, Espejo-Mojica ÁJ, Ardila A, Pulido N, Reyes M, et al. Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years' experience from a reference center. Orphanet J Rare Dis. 2018;13(1):141. doi:10.1186/s13023-018-0879-2.6. Orphanet. Tyrosinemia type 2 [Internet]. Paris: Orphanet; 2023 [cited 2024 Dec 18]. Available from: https://www.orpha.net/en/disease/detail/283787. Beyzaei Z, Nabavizadeh S, Karimzadeh S, Geramizadeh B. The mutation spectrum and ethnic distribution of non-hepatorenal tyrosinemia (types II, III). Orphanet J Rare Dis. 2022;17(1):424. https://doi.org/10.1186/s13023-022-02579-08. Bayzaei Z, Dehghani SM, Geramizadeh B. Tyrosinemia Type II. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025 [updated 2024 Oct 24; cited 2024 Dic 06]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK608431/9. Peña-Quintana L, Scherer G, Curbelo-Estévez ML, et al. Tyrosinemia Type II: mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation. Clin Genet. 2017;92(3):306–17. doi:10.1111/cge.1300310. van Spronsen FJ, Burlina A, Dionisi Vici C. Tyrosine metabolism. In: Blau N, Dionisi Vici C, Ferreira CR, Vianey-Saban C, van Karnebeek CDM, editors. Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Cham: Springer; 2022. p. 1–20. doi:10.1007/978-3-030-67727-5_21.11. Bose S, Mandal S, Khan R, Maji HS, Ashique S. Current landscape on development of phenylalanine and toxicity of its metabolites - a review. Curr Drug Saf. 2024;19(2):208-217. doi:10.2174/1574886318666230331112800.12. Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H. Aminoacidopathies: prevalence, etiology, screening, and treatment options. Biochem Genet. 2018;56(1-2):7-21. doi:10.1007/s10528-017-9825-6.13. Meléndrez-Vásquez D, Ossa Trujillo RH, Zarante-Bahamón AM, Rojas JA, Tamayo M. Palmo-plantar keratoderma secondary to tyrosinemia type II. Piel. 2024. doi:10.1016/j.piel.2024.04.005.14. Gliagias V, Denisova K, Kang JJ. A child with dendritiform eye lesions and developmental delay. Am J Ophthalmol Case Rep. 2022;28:101701. doi:10.1016/j.ajoc.2022.101701.15. Locatelli F, Puzenat E, Arnoux JB, Blanc D, Aubin F. Richner-Hanhart syndrome (tyrosinemia type II). Cutis. 2017;100(6):E20–2.16. Miranda BA, Rocha ACH, Arantes RR, Kanufre VC, Silva SC, Vasconcelos-Santos DV. Bilateral recurrent pseudodendritic keratopathy as the initial manifestation of tyrosinemia type II. Ophthalmic Genet. 2022;43(2):282–4. doi:10.1080/13816810.2022.203416817. Daly A, Adam S, Allen H, Ash J, Dale C, Dixon M, et al. UK dietary practices for tyrosinaemias: time for change. Nutrients. 2022;14(24):5202. doi:10.3390/nu1424520218. Delsoglio M, Capener R, MacDonald A, Daly A, Ashmore C, Donald S, et al. Evaluation of a new 'mix-in' style glycomacropeptide-based protein substitute for food and drinks in patients with phenylketonuria and tyrosinemia. Nutrients. 2023;15(16):3598. doi:10.3390/nu1516359819. Peacock DJSJ, Ferreira CR, Horvath G, Hoffmann GF, Blau N, Ebrahimi-Fakhari D. Clinical and biochemical footprints of inherited metabolic diseases: Ia. Movement disorders, updated. Mol Genet Metab. 2025;145(1):109084. doi:10.1016/j.ymgme.2025.10908420. Carvalho-Silva M, Gomes LM, Scaini G, Rebelo J, Damiani AP, Pereira M, et al. Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II. Metab Brain Dis. 2017;32(4):1043–50.21. Antonini R, Scaini G, Michels M, Matias MBD, Schuck PF, Ferreira GC, et al. Effects of omega-3 fatty acids supplementation on inflammatory parameters after chronic administration of L-tyrosine. Metab Brain Dis. 2020;35(2):295–303.22. Thibault LP, Mitchell GA, Parisien B, Hamel P, Blanchard AC. An infant with bilateral keratitis: From infectious to genetic diagnosis. Am J Case Rep. 2022;23:e937967.23. Teodorak BP, Scaini G, Carvalho-Silva M, Gomes LM, Teixeira LJ, Rebelo J, De Prá SD, Zeni N, Schuck PF, Ferreira GC, Streck EL. Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L-tyrosine. Metab Brain Dis. 2017;32(2):557–64.24. Carvalho-Silva M, Gomes LM, Gomes ML, Ferreira BK, Schuck PF, Ferreira GC, Dal-Pizzol F, de Oliveira J, Scaini G, Streck EL. Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats. Metab Brain Dis. 2019;34(4):1207–1219. doi:10.1007/s11011-019-00411-6.25. Gomes LM, Scaini G, Carvalho-Silva M, Gomes ML, Malgarin F, Kist LW, Bogo MR, Rico EP, Zugno AI, Deroza PFP, Réus GZ, de Moura AB, Quevedo J, Ferreira GC, Schuck PF, Streck EL. Antioxidants reverse the changes in the cholinergic system caused by L-tyrosine administration in rats. Neurotox Res. 2018;34(4):769–780. doi:10.1007/s12640-018-9866-6.26. Manta-Vogli PD, Schulpis KH, Dotsikas Y, Loukas YL. Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs). J Pediatr Endocrinol Metab. 2020;33(1):5–20. doi:10.1515/jpem-2019-0048.27. Saudubray JM, Baumgartner MR, García-Cazorla Á, Walter J. Disorders of Tyrosine Metabolism. In: Inborn Metabolic Diseases: Diagnosis and Treatment [Internet]. Berlin: Springer; 2022 [cited 2025 May 25]. Available from: https://research.ebsco.com/linkprocessor/plink?id=8428acb6-e645-3321-bea2-c53ebfc81a4e.28. Martin GC, de Lonlay P, Chapron T, Cochereau I, Caputo G, Gabison E. Bilateral dendriform ulcer leading to an early diagnosis of tyrosinemia type 2. J AAPOS. 2020;24(2):120–2. doi:10.1016/j.jaapos.2019.12.007.29. Mohite AA, Abbott J. Photophobia accompanied by painful plantar punctate hyperkeratotic patches: Tyrosinemia type 2. Indian J Ophthalmol. 2018 Mar;66(3):449. doi:10.4103/ijo.ijo_820_17. PMID: 29480263; PMCID: PMC5859607.30. Ghalamkarpour F, Niknezhad N, Niknejad N. Familial Richner-Hanhart syndrome: Report of a sibling with incomplete presentation. Dermatol Ther. 2020;33(6):e14072. doi:10.1111/dth.14072.31. da Silva ISF, Sopa I, Gomes D, Peixoto L, Oliveira A. From skin lesions to tyrosinemia type II diagnosis. J Inherit Metab Dis. 2024;47(5):1107–1108. doi:10.1002/jimd.12720.32. Streck EL, De Prá SDT, Ferro PR, Carvalho-Silva M, Gomes LM, Agostini JF, Damiani A, Andrade VM, Schuck PF, Ferreira GC, Scaini G. Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II. Mol Cell Biochem. 2017;435(1-2):207–214. doi:10.1007/s11010-017-3070-5.33. Hannah-Shmouni F, MacNeil L, Lara-Corrales I, Pope E, Kannu P, Sondheimer N. Whole-exome sequencing identifies a homozygous pathogenic variant in TAT in a girl with palmoplantar keratoderma. Mol Genet Metab Rep. 2019;21:100534. doi:10.1016/j.ymgmr.2019.100534.34. Soares DC, Stroparo MN, Lian YC, Takakura CY, Wolf S, Betz R, Kim CA. Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome. J Inherit Metab Dis. 2017;40(3):461–462. doi:10.1007/s10545-016-9996-z.35. Chakrapani A, Gissen P, McKiernan P. Inborn Metabolic Diseases: Diagnosis and Treatment. Chapter 17: Disorders of Tyrosine Metabolism [Internet]. Berlin: Springer; 2022 [cited 2025 May 25]. Available from: http://ndl.ethernet.edu.et/bitstream/123456789/55539/1/50.pdf36. Rupec RA. Braun-Falco's Dermatology. Chapter 91: Disorders of Purine, Sphingolipid, and Amino Acid Metabolism [Internet]. Berlin, Heidelberg: Springer; 2022 [cited 2025 May 25]. Available from: https://research.ebsco.com/linkprocessor/plink?id=f7c5abb8-69b4-392b-b182-fa91c23dfa4137. Al Jasmi F, Galadari H, Clayton PT, Footitt EJ. Metabolic disorders and the skin. In: Hoeger P, Kinsler V, Yan A, Harper J, Oranje A, Bodemer C, Larralde M, Luk D, Mendiratta V, Purvis D, editors. Harper's Textbook of Pediatric Dermatology [Internet]. Chichester, UK: Wiley-Blackwell; 2019 [cited 2025 May 25]. Available from: https://doi.org/10.1002/9781119142812.ch15238. Khochtali S, Daldoul N, Zina S, Kadri A, Ben Yahia S, Khairallah M. Atteinte cornéenne liée à une tyrosinémie de type II mimant une kératite herpétique: à propos d’un cas chez un adulte. J Fr Ophtalmol. 2018;41(7):e315–e318. https://doi.org/10.1016/j.jfo.2017.09.02839. Alsharhan H, Ficicioglu C. Disorders of phenylalanine and tyrosine metabolism. Transl Sci Rare Dis. 2020;5(1–2):3–58. doi:10.3233/TRD-20004940. Aliu E, Kanungo S, Arnold G. Amino acid disorders. Ann Transl Med. 2018;6(24):471. doi:10.21037/atm.2018.12.1241. Marek S, Linaburg T, Nguyen BJ. Inborn errors of metabolism and their corneal manifestations. Adv Ophthalmol Optom. 2023;8(1):329–41. doi:10.1016/j.yaoo.2023.02.015.42. Jones P, Patel K, Rakheja D. Disorder: Tyrosinemia types 2 and 3. In: Jones P, Patel K, Rakheja D, editors. A Quick Guide to Metabolic Disease Testing Interpretation. 2nd ed. Academic Press; 2020. p. 127–30. doi:10.1016/B978-0-12-816926-1.00024-9.43. Rosenberg RN, Pascual JM. Inborn errors of amino acid metabolism. In: Rosenberg RN, Pascual JM, editors. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. 7th ed. Academic Press; 2025. p. 761–77. doi:10.1016/B978-0-443-19041-4.00046-7.44. Chirita-Emandi A. Screening for inborn errors of metabolism. In: DE Caterina R, Martinez JA, Kohlmeier M, editors. Principles of Nutrigenetics and Nutrigenomics. Academic Press; 2020. p. 153–8. doi:10.1016/B978-0-12-804572-5.00019-7.45. van Karnebeek CDM, Berry-Kravis E, Gropman A. Treatment of neurodevelopmental disorders. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, Pearl PL, Shevell MI, editors. Swaiman's Pediatric Neurology. 6th ed. Elsevier; 2017. p. 478–88. doi:10.1016/B978-0-323-37101-8.00059-X.46. Tseng LA, Sowerbutt C, Lee JJY, van Karnebeek CDM. P4 medicine for epilepsy and intellectual disability: nutritional therapy for inherited metabolic disease. Emerg Top Life Sci. 2019;3(1):75–95. doi:10.1042/ETLS20180180.47. Dalili S, Talea A, Aghajany-Nasab M, Miandoab NAA, Koohmanaee S, Hakemzadeh ST, Medghalchi N. Clinical features and laboratory diagnosis of aminoacidopathies: a narrative review. 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