Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet
Introduction: Tyrosinemia Type 1 (HT1) is an autosomal recessive disorder caused by a defect in the enzyme fumarylacetoacetate hydroxylase in the tyrosine pathway. Implementation of nitisinone (NTBC) treatment has dramatically improved survival rate of individuals with HT1, yet recent reports on cog...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426916301197 |
| _version_ | 1818203199119556608 |
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| author | María Ignacia García Alicia de la Parra Carolina Arias Miguel Arredondo Juan Francisco Cabello |
| author_facet | María Ignacia García Alicia de la Parra Carolina Arias Miguel Arredondo Juan Francisco Cabello |
| author_sort | María Ignacia García |
| collection | DOAJ |
| description | Introduction: Tyrosinemia Type 1 (HT1) is an autosomal recessive disorder caused by a defect in the enzyme fumarylacetoacetate hydroxylase in the tyrosine pathway. Implementation of nitisinone (NTBC) treatment has dramatically improved survival rate of individuals with HT1, yet recent reports on cognitive impairment in treated patients exist.
Aims: Describe long-term neurocognitive outcome individuals with HT1 treated with nitisinone and protein restricted diet.
Methodology: Twelve individuals with HT1 were analyzed with respect to psychomotor development and cognitive functioning using standardized psychometric tests. Plasma tyrosine and phenylalanine concentrations were also collected and analyzed, as part of the regular HT1 follow up program in our clinic.
Results: Delayed performance in Bayley scale mental developmental index (MDI) was identified in 29% to 38% of the patients assessed at different ages. At preschool age, mean full scale IQ (FSIQ) was 88 ± 16; six out of nine assessed children preformed within normal range, and one child presented with intellectual disability. At school age mean FSIQ was 79 ± 18, three out of nine children preformed within normal range and two showed intellectual disability. Repeated measures showed IQ decline over time in four out of eight patients, all of whom presented with symptoms in their first months of life. Patients that showed no progressive IQ decline were 8 months or older at diagnosis, with a mean age of 17 months. Significant correlation between Phe/Tyr ratio and FSIQ at school age was identified (r = −0.689; p < 0.044).
Conclusion: Some patients with HT1 treated with nitisinone and protein restricted diet are at risk of presenting developmental delay and impaired cognitive functioning. Patients with early onset of symptoms could be at risk for progressive cognitive functioning decline over time. |
| first_indexed | 2024-12-12T03:21:32Z |
| format | Article |
| id | doaj.art-7d4e5fed871a424cb2d48a424c10cc4d |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-12T03:21:32Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-7d4e5fed871a424cb2d48a424c10cc4d2022-12-22T00:40:09ZengElsevierMolecular Genetics and Metabolism Reports2214-42692017-06-0111C121610.1016/j.ymgmr.2017.01.016Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted dietMaría Ignacia García0Alicia de la Parra1Carolina Arias2Miguel Arredondo3Juan Francisco Cabello4Laboratory of Genetics and Metabolic Disease, INTA, University of Chile, ChileLaboratory of Genetics and Metabolic Disease, INTA, University of Chile, ChileLaboratory of Genetics and Metabolic Disease, INTA, University of Chile, ChileLaboratory of Micronutrients, INTA, University of Chile, ChileLaboratory of Genetics and Metabolic Disease, INTA, University of Chile, ChileIntroduction: Tyrosinemia Type 1 (HT1) is an autosomal recessive disorder caused by a defect in the enzyme fumarylacetoacetate hydroxylase in the tyrosine pathway. Implementation of nitisinone (NTBC) treatment has dramatically improved survival rate of individuals with HT1, yet recent reports on cognitive impairment in treated patients exist. Aims: Describe long-term neurocognitive outcome individuals with HT1 treated with nitisinone and protein restricted diet. Methodology: Twelve individuals with HT1 were analyzed with respect to psychomotor development and cognitive functioning using standardized psychometric tests. Plasma tyrosine and phenylalanine concentrations were also collected and analyzed, as part of the regular HT1 follow up program in our clinic. Results: Delayed performance in Bayley scale mental developmental index (MDI) was identified in 29% to 38% of the patients assessed at different ages. At preschool age, mean full scale IQ (FSIQ) was 88 ± 16; six out of nine assessed children preformed within normal range, and one child presented with intellectual disability. At school age mean FSIQ was 79 ± 18, three out of nine children preformed within normal range and two showed intellectual disability. Repeated measures showed IQ decline over time in four out of eight patients, all of whom presented with symptoms in their first months of life. Patients that showed no progressive IQ decline were 8 months or older at diagnosis, with a mean age of 17 months. Significant correlation between Phe/Tyr ratio and FSIQ at school age was identified (r = −0.689; p < 0.044). Conclusion: Some patients with HT1 treated with nitisinone and protein restricted diet are at risk of presenting developmental delay and impaired cognitive functioning. Patients with early onset of symptoms could be at risk for progressive cognitive functioning decline over time.http://www.sciencedirect.com/science/article/pii/S2214426916301197Tyrosinemia type 1NitisinoneNTBCTyrosineCognitive impairment |
| spellingShingle | María Ignacia García Alicia de la Parra Carolina Arias Miguel Arredondo Juan Francisco Cabello Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet Molecular Genetics and Metabolism Reports Tyrosinemia type 1 Nitisinone NTBC Tyrosine Cognitive impairment |
| title | Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet |
| title_full | Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet |
| title_fullStr | Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet |
| title_full_unstemmed | Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet |
| title_short | Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet |
| title_sort | long term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein restricted diet |
| topic | Tyrosinemia type 1 Nitisinone NTBC Tyrosine Cognitive impairment |
| url | http://www.sciencedirect.com/science/article/pii/S2214426916301197 |
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