IntroductionTyrosinemia 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.AimsDescribe long-term neurocognitive outcome individuals with HT1 treated with nitisinone and protein restricted diet.MethodologyTwelve 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.ResultsDelayed 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).ConclusionSome 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.

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IntroductionPhenylketonuria (PKU) is an autosomal recessive disorder characterized by a deficiency in phenylalanine (Phe) hydroxylase activity. Early diagnosis and continuous treatment with a low Phe diet prevents severe neurological and cognitive impairment.Aims1. Analyze how treatment adherence evolves through infancy, childhood, and early adolescence in individuals with PKU. 2. Identify early signs of treatment discontinuation.MethodologyThis longitudinal, retrospective study included 75 children diagnosed through newborn screening, ages 7 to 13 years. Data on blood Phe concentration, number of blood samples sent, proportion of samples with Phe concentrations over the recommended range, and number of visits to the metabolism clinic were recorded. Logistic regression analysis was used to identify the variables that predict treatment discontinuation before 13 years of age.ResultsA progressive increase in mean blood Phe concentrations with age was identified. The greatest increase occurred between the first and second years of life. By age ten, mean Phe blood concentration of the group was above the recommended range. The proportion of samples with Phe concentrations over the recommended range also increased with age, from an average of 13% during the first year of life to 67% in early adolescence. Sixty-eight percent of the children attended the outpatient clinic and sent samples from birth to the time of the study. Individuals who discontinued follow-up showed significantly higher mean blood Phe concentrations (360 vs. 220.9 μmol/L; p = 0.004) and the proportion of samples over the recommended range (37% vs. 12% p = 0.002) was significantly higher during the second year of life. Mean age for children who discontinued treatment was 5.5 years of age. Blood Phe concentration values at 12 to 23 months of age and at 6 to 8 years of age significantly predicted treatment discontinuation before 13 years of age.ConclusionTreatment adherence in PKU diminishes with age. Early signs of treatment discontinuation can be identified during the second year of life, allowing preventive interventions in high risk groups.

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