{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:13:01Z","timestamp":1775815981379,"version":"3.50.1"},"reference-count":21,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. paul. pediatr."],"abstract":"<jats:p>ABSTRACT  Objective:  Tyrosinemia type III (HT III) is the rarest form of tyrosinemia, and the full clinical spectrum of this disorder is still unknown. The neurological involvement varies, including intellectual impairment and attention deficit disorder with hyperactivity (ADHD). We report the case of two siblings diagnosed with HT III at different ages.  Case description:  The index case was diagnosed by newborn screening for endocrine and metabolic disorders, starting a low-protein diet immediately, with a consistent decrease in tyrosine levels. By the age of three, the child displayed a hyperactive behavior, starting treatment for ADHD two years later. At seven years of age, he shows a slight improvement in terms of behavior and attention span and has a cognitive performance slightly lower than his peers, despite maintaining acceptable tyrosine levels. His sister, who had a history of ADHD since age five, was diagnosed with HT III after family screening at the age of eight. Despite initiating a dietetic treatment, her behavior did not improve, and she has a mild intellectual impairment.  Comments:  This is the first case report describing siblings with HT III who underwent nutritional treatment with a low-protein diet in different phases of life, with a better neurological and behavioral evaluation in the patient who started treatment earlier.<\/jats:p>","DOI":"10.1590\/1984-0462\/2020\/38\/2018158","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T15:33:05Z","timestamp":1591371185000},"source":"Crossref","is-referenced-by-count":17,"title":["TYROSINEMIA TYPE III: A CASE REPORT OF SIBLINGS AND LITERATURE REVIEW"],"prefix":"10.1590","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2708-0165","authenticated-orcid":false,"given":"F\u00e1bio","family":"Barroso","sequence":"first","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-6840","authenticated-orcid":false,"given":"Joana","family":"Correia","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1203-8180","authenticated-orcid":false,"given":"Anabela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-4016","authenticated-orcid":false,"given":"Carla","family":"Carmona","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-779X","authenticated-orcid":false,"given":"Laura","family":"Vilarinho","sequence":"additional","affiliation":[{"name":"National Institute of Health,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-1314","authenticated-orcid":false,"given":"Manuela","family":"Almeida","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9247-9391","authenticated-orcid":false,"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio do Porto,  Portugal"}]}],"member":"530","published-online":{"date-parts":[[2020]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s100240010146","article-title":"Tyrosinemia: a review","volume":"4","author":"Russo PA","year":"2001","journal-title":"Pediatr Dev Pathol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1023\/A:1013936107064","article-title":"Outcome of tyrosinemia type III","volume":"24","author":"Ellaway CJ","year":"2001","journal-title":"J Inherit Metab Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/j.1651-2227.1997.tb15192.x","article-title":"Tyrosinemia type III: diagnosis and ten-year follow-up","volume":"86","author":"Cerone R","year":"1997","journal-title":"Acta Paediatr"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ymgmr.2015.10.004","article-title":"Tyrosinemia type III in an asymptomatic girl","volume":"5","author":"Szymanska E","year":"2015","journal-title":"Mol Genet Metab Rep"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11011-011-9255-9","article-title":"Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats","volume":"26","author":"Andrade RB","year":"2011","journal-title":"Metab Brain Dis"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1007\/s11064-013-1180-3","article-title":"Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats","volume":"38","author":"Macedo LG","year":"2013","journal-title":"Neurochem Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s11064-013-1207-9","article-title":"L-tyrosine induces DNA damage in brain and blood of rats","volume":"39","author":"De Pr\u00e1 SD","year":"2014","journal-title":"Neurochem Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s11011-016-9936-5","article-title":"Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L.-tyrosine","volume":"32","author":"Teodorak BP","year":"2017","journal-title":"Metab Brain Dis"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.biopha.2008.06.030","article-title":"Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III","volume":"63","author":"D\u2019Eufemia P","year":"2009","journal-title":"Biomed Pharmacother"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ymgme.2012.09.002","article-title":"Tyrosinemia Type III detected via neonatal screening: management and outcome","volume":"107","author":"Heylen E","year":"2012","journal-title":"Mol Genet Metab"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00787-016-0908-4","article-title":"Can psychiatric childhood disorders be due to inborn errors of metabolism?","volume":"26","author":"Simons A","year":"2017","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"ref12","first-page":"32","article-title":"A new case of tyrosinemia type III detected by neonatal screening","volume":"19","author":"Preece MA","year":"1996","journal-title":"J Inherit Metab Dis"},{"key":"ref13","first-page":"25","article-title":"Tyrosinemia type III detected by neonatal screening","volume":"21","author":"Standing SJ","year":"1998","journal-title":"J Inherit Metab Dis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s004390000307","article-title":"Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III","volume":"106","author":"R\u00fcetschi U","year":"2000","journal-title":"Hum Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1023\/A:1013936107064","article-title":"Outcome of tyrosinemia type III","volume":"24","author":"Ellaway CJ","year":"2001","journal-title":"J Inherit Metab Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1203\/00006450-198302000-00002","article-title":"Four-Hydroxyphenylpyruvic acid oxidase de\u00a2ciency with normal fumarylacetoacetase: a new variant of hereditary hypertyrosinaemia","volume":"17","author":"Endo F","year":"1983","journal-title":"Pediatr Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1203\/00006450-198301000-00005","article-title":"Chronic tyrosinemia associated with 4-hydroxyphenylpyruvate dioxygenase deficiency with acute intermittent ataxia and without visceral and bone involvement","volume":"17","author":"Giardini O","year":"1983","journal-title":"Pediatr Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/BF01800222","article-title":"Autoimmune thyroiditis in a case of tyrosinemia III","volume":"15","author":"D\u2019Eufemia P","year":"1992","journal-title":"J Inherit Metab Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF00710429","article-title":"Immunological abnormalities in a patient with tyrosinemia type III","volume":"18","author":"D\u2019Eufemia 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