2026-04-17T03:26:04Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/51302025-10-24T10:31:55Zcom_2072_378070com_2072_378040col_2072_378092
2025-10-24T10:31:55Z
urn:hdl:11351/5130
Evolution of tyrosinemia type 1 disease in patients treated with nitisinone in Spain
Sánchez-Pintos, Paula
Aldámiz-Echevarría, Luís
Vitoria, Isidro
Navas-López, Víctor Manuel
Pintos Morell, Guillem
Couce, Maria Luz
Martín-Hernández, Elena
Tiroide - Malalties
Ciclohexà
Qualitat de vida
DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Amino Acid Metabolism, Inborn Errors::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Tyrosinemias
/complications
CHEMICALS AND DRUGS::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclohexanes::Cyclohexanones
/therapeutic use
HEALTH CARE::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Health Status::Quality of Life
ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::enfermedades cerebrales metabólicas congénitas::tirosinemias
/complicaciones
COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::hidrocarburos::hidrocarburos cíclicos::hidrocarburos alicíclicos::cicloparafinas::ciclohexanos::ciclohexanonas
/uso terapéutico
ATENCIÓN DE SALUD::ambiente y salud pública::salud pública::medidas epidemiológicas::demografía::estado de salud::calidad de vida
Nephrocalcinosis; Phenotype; Severe liver dysfunction
Nefrocalcinosis; Fenotipo; Disfunción hepática grave
Nefrocalcinosi; Fenotip; Disfunció hepàtica greu
Treatment with nitisinone (NTBC) has brought about a drastic improvement in the treatment and prognosis of hereditary tyrosinemia type I (HT1). We conducted a retrospective observational multicentric study in Spanish HT1 patients treated with NTBC to assess clinical and biochemical long-term evolution.We evaluated 52 patients, 7 adults and 45 children, treated with NTBC considering: age at diagnosis, diagnosis by clinical symptoms, or by newborn screening (NBS); phenotype (acute/subacute/chronic), mutational analysis; symptoms at diagnosis and clinical course; biochemical markers; doses of NTBC; treatment adherence; anthropometric evolution; and neurocognitive outcome.The average follow-up period was 6.1 ± 4.9 and 10.6 ± 5.4 years in patients with early and late diagnosis respectively. All patients received NTBC from diagnosis with an average dose of 0.82 mg/kg/d. All NBS-patients (n = 8) were asymptomatic at diagnosis except 1 case with acute liver failure, and all remain free of liver and renal disease in follow-up. Liver and renal affectation was markedly more frequent at diagnosis in patients with late diagnosis (P < .001 and .03, respectively), with ulterior positive hepatic and renal course in 86.4% and 93.2% of no-NBS patients, although 1 patient with good metabolic control developed hepatocarcinoma.Despite a satisfactory global nutritional evolution, 46.1% of patients showed overweight/obesity. Interestingly lower body mass index was observed in patients with good dietary adherence (20.40 ± 4.43 vs 24.30 ± 6.10; P = .08) and those with good pharmacological adherence (21.19 ± 4.68 vs 28.58 ± 213.79).intellectual quotient was ≥85 in all NBS- and 68.75% of late diagnosis cases evaluated, 15% of which need pedagogical support, and 6.8% (3/44) showed school failure.Among the 12 variants identified in fumarylacetoacetate hydrolase gene, 1 of them novel (H63D), the most prevalent in Spanish population is c.554-1 G>T.After NTBC treatment a reduction in tyrosine and alpha-fetoprotein levels was observed in all the study groups, significant for alpha-fetoprotein in no NBS-group (P = .03), especially in subacute/chronic forms (P = .018).This series confirms that NTBC treatment had clearly improved the prognosis and quality of life of HT1 patients, but it also shows frequent cognitive dysfunctions and learning difficulties in medium-term follow-up, and, in a novel way, a high percentage of overweight/obesity.
2025-10-24T10:31:55Z
2025-10-24T10:31:55Z
2020-07-31T13:05:37Z
2020-07-31T13:05:37Z
2019-09-01
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://hdl.handle.net/11351/5130
Medicine;98(39)
https://journals.lww.com/md-journal/FullText/2019/09270/Evolution_of_tyrosinemia_type_1_disease_in.66.aspx
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Wolters Kluwer Health, Inc.
Scientia