There is substantial evidence in the literature that patients with cystic fibrosis (CF) have higher oxidative stress than patients with other diseases or healthy subjects. This results in an increase in reactive oxygen species (ROS) and in a deficit of antioxidant molecules and plays a fundamental role in the progression of chronic lung damage. Although it is known that recurrent infection–inflammation cycles in CF patients generate a highly oxidative environment, numerous clinical and preclinical studies suggest that the airways of a patient with CF present an inherently abnormal proinflammatory milieu due to elevated oxidative stress and abnormal lipid metabolism even before they become infected. This could be directly related to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency, which appears to produce a redox imbalance in epithelial cells and extracellular fluids. This review aims to summarize the main mechanism by which CFTR deficiency is intrinsically responsible for the proinflammatory environment that characterizes the lung of a patient with CF.

In the literature, deletions in the 2p16.3 region of the neurexin gene (NRXN1) are associated with cognitive impairment, and other neuropsychiatric disorders, such as schizophrenia, autism, and Pitt–Hopkins-like syndrome 2. In this paper, we present twins with deletion 2p16.3 of the NRXN1 gene using a comparative genomic hybridization array. The two children had a dual diagnosis consisting of mild cognitive impairment and neurodevelopmental delay. Furthermore, they showed a dysmorphic phenotype characterized by facio-cranial disproportion, turricephalus, macrocrania, macrosomia, strabismus, and abnormal conformation of both auricles with low implantation. The genetic analysis of the family members showed the presence, in the father’s genetic test, of a microdeletion of the short arm of chromosome 2, in the 2p16.3 region. Our case report can expand the knowledge on the genotype–phenotype association in carriers of 2p16.3 deletion and for genetic counseling that could help in the prevention and eventual treatment of this genetic condition. Newborn carriers should undergo neurobehavioral follow-ups for timely detection of warning signs.

Background: Phenylketonuria (PKU) is a rare autosomal recessive metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to hyperphenylalaninemia (HPA). Untreated, elevated phenylalanine (Phe) levels cause severe neurocognitive, developmental, and psychiatric complications. Management relies on a Phe-restricted diet, which is challenging to maintain, particularly in adolescents and adults. Sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), can enhance residual PAH activity, lowering blood Phe levels and increasing dietary tolerance in responsive patients. However, real-world alignment with best practices remains underexplored. This study aims to report a tertiary referral center’s experience with sapropterin treatment in PKU and assess adherence to international guidelines. Methods: We retrospectively analyzed 23 PKU patients treated with sapropterin from 2007 to 2025. Patients with baseline Phe levels of 360–2000 µmol/L underwent a 10 mg/kg/day loading test over two weeks. Responsiveness was defined as a ≥30% reduction in blood Phe levels. Phe levels were measured pre- and post-test, and dietary tolerance was evaluated. Adherence to best practices was critically reviewed. Results: All patients showed significant Phe reductions (mean 71.43%, p < 0.0001), exceeding responsiveness thresholds. Most achieved substantial increases in dietary Phe tolerance, with three patients partially responsive (800–1200 mg/day). Responsiveness was unrespectful of the patient’s genotype, for those individuals for whom this was known (8/23 patients). Although effective, the test dose and duration differed from guideline recommendations (20 mg/kg/day). Neuropsychological and QoL assessments were not systematically performed, representing a key limitation. Conclusions: Sapropterin dihydrochloride effectively identified responders and improved dietary flexibility even with lower dosing protocols. Greater adherence to international standards, particularly regarding long-term neuropsychological monitoring, is needed to optimize patient care.