RESUMO
Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene and is characterized by altered amino acid metabolism. More than 1500 known PAH variants intricately determine a spectrum of metabolic phenotypes. We aim to report on clinical presentation and PAH variants identified in 23 hyperphenylalaninemia (HPA)/PKU Romanian patients. Our cohort exhibited classic PKU (73.9%, 17/23), mild PKU (17.4%, 4/23), and mild HPA (8.7%, 2/23). Severe central nervous system sequelae are frequent in our cohort in late-diagnosis symptomatic patients, which highlights yet again the significance of an early dietary treatment, neonatal screening and diagnosis, and facilitated access to treatment. Next-generation sequencing (NGS) identified a total of 11 PAH pathogenic variants, all previously reported, mostly missense changes (7/11) in important catalytic domains. c.1222C>T p.Arg408Trp was the most frequent variant, with an allele frequency of 56.5%. Twelve distinct genotypes were identified, the most frequent of which was p.Arg408Trp/p.Arg408Trp (34.8%, 8/23). Compound heterozygous genotypes were common (13/23), three of which had not been previously reported to the best of our knowledge; two correlated with cPKU and one showed an mPKU phenotype. Generally, there are genotype-phenotype correlation overlaps with the public data reported in BIOPKUdb; as our study shows, clinical correlates are subject to variation, in part due to uncontrolled or unknown epigenetic or environmental regulatory factors. We highlight the importance of establishing the genotype on top of using blood phenylalanine levels.
RESUMO
Background and Objectives: Characterization of patients with endocarditis regarding demographic, clinical, biological and imagistic data, blood culture results and possible correlation between different etiologic factors and host status characteristics. Material and methods: This is a retrospective observational descriptive study conducted on patients older than 18 years admitted in the past 10 years, in the Cardiology Clinic of the Clinical County Emergency Hospital Oradea Romania, with clinical suspicion of bacterial endocarditis. Demographic data, clinical, paraclinical investigations and outcome were registered and analyzed. Results: 92 patients with definite infective endocarditis (IE) according to modified Duke criteria were included. The mean age of patients was 63.80 ± 13.45 years. A percent of 32.6% had health care associated invasive procedure performed in the 6 months before diagnosis of endocarditis. Charlson's comorbidity index number was 3.53 ± 2.029. Most common clinical symptoms and signs were: shortness of breath, cardiac murmur, fever. Sixty-six patients had native valve endocarditis, 26 patients had prosthetic valve endocarditis and one patient was with congenital heart disease. Blood cultures were positive in 61 patients. Among positive culture patient's staphylococcus group was the most frequently involved: Staphylococcus aureus (19.6%) and coagulase negative Staphylococcus (18.5%). Most frequent complications were heart failure, acute renal failure and embolic events. Conclusions: Staphylococcus aureus IE was associated with the presence of large vegetations, prosthetic valve endocarditis and intracardiac abscess. Coagulase negative Staphylococcus (CoNS) infection was associated with prosthetic valve dysfunction. Streptococcus gallolyticus etiology correlated with ischemic embolic stroke and the presence of large vegetations. Cardiovascular surgery was recommended in 67.4% of patients but was performed only on half of them. In hospital death occurred in 33.7% of patients and independent predictors of mortality were congestive heart failure and septic shock.
