Browsing by Author "Fonseca, H"
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- Phenylketonuria in Portugal: Genotype–Phenotype Correlations Using Molecular, Biochemical, and Haplotypic AnalysesPublication . Ferreira, F; Azevedo, L; Neiva, R; Sousa, C; Fonseca, H; Marcão, A; Rocha, H; Carmona, C; Ramos, S; Bandeira, A; Martins, E; Campos, T; Rodrigues, E; Garcia, P; Diogo, L; Ferreira, AC; Sequeira, S; Silva, F; Rodrigues, L; Gaspar, A; Janeiro, P; Amorim, A; Vilarinho, LBackground: The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease. Methods: In this report, the biochemical and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) are presented. Results: Overall, the results show that a high overlap exists between different types of variants and phenylalanine levels. Molecular analyses reveal a wide mutational spectrum in our population with a total of 56 previously reported variants, most of them found in compound heterozygosity (74% of the patients). Intragenic polymorphic markers were used to assess the haplotypic structure of mutated chromosomes for the most frequent variants found in homozygosity in our population (p.Ile65Thr, p.Arg158Gln, p.Leu249Phe, p.Arg261Gln, p.Val388Met, and c.1066-11G>A). Conclusion: Our data reveal high heterogeneity at the biochemical and molecular levels and are expected to provide a better understanding of the molecular basis of this disease and to provide clues to elucidate genotype-phenotype correlations.
- Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic AnalysesPublication . Ferreira, F; Azevedo, L; Neiva, R; Sousa, C; Fonseca, H; Marcão, A; Rocha, H; Carmona, C; Ramos, S; Bandeira, A; Martins, E; Campos, T; Rodrigues, E; Garcia, P; Diogo, L; Ferreira, AC; Sequeira, S; Silva, F; Rodrigues, L; Gaspar, A; Janeiro, P; Amorim, A; Vilarinho, LThe impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.
- Systolic Time Ratio Measured by Impedance Cardiography Accurately Screens Left Ventricular Diastolic Dysfunction in Patients with Arterial HypertensionPublication . Nazário Leão, R; Marques da Silva, P; Branco, LM; Fonseca, H; Bento, B; Alves, M; Virella, D; Palma Reis, RBACKGROUND: The use of impedance cardiography (ICG) may play a role in the assessment of cardiac effects of hypertension (HT), especially its hemodynamic features. Hypertensive heart disease involves structural changes and alterations in left ventricular geometry that end up causing systolic and/or diastolic dysfunction. The IMPEDDANS study aims to assess the usefulness of ICG for the screening of left ventricular diastolic dysfunction (LVDD) in patients with HT. METHODS: Patients with HT were assessed by echocardiography and ICG. Receiver-operating characteristic curve and the area under the curve were used to assess the discriminative ability of the parameters obtained by ICG to identify LVDD, as diagnosed by echocardiography. RESULTS: ICG derived pre-ejection period (PEP), left ventricle ejection time (LVET), systolic time ratio (STR) and D wave were associated (p < 0.001) with LVDD diagnosis, with good discriminative ability: PEP (AUC 0.81; 95% CI 0.74-0.89), LVET (AUC 0.82; 95% CI 0.75-0.88), STR (AUC 0.97; 95% CI 0.94-1.00) and presence of D wave (AUC = 0.87; 95% CI 0.82-0.93). STR ≥ 0.30 outperformed the other parameters (sensitivity of 98.0%, specificity of 90.2%, positive predictive value of 95.2%, and negative predictive value of 96.1%). CONCLUSION: The ICG derived value of STR allows the accurate screening of LVDD in patients with HT. It might as well be used for follow up assessment. TRIAL REGISTRATION: The study protocol was retrospectively registered as IMPEDDANS on ClinicalTrials.gov (ID: NCT03209141) on July 6, 2017.