1,721,115 research outputs found
Delphi panel experts’ group; Spagnoli C. Aromatic L-amino Acid Decarboxylase (AADC) deficiency: results from an Italian modified Delphi consensus
No full textA new strategy of desensitization in mucopolysaccharidosis type II disease treated with idursulfase therapy: A case report and review of the literature
Full text linkMucopolysaccharidosis type II (MPS II) is a multisystemic lysosomal storage disorder caused by deficiency of the iduronate 2-sulfatase enzyme. Currently, enzyme replacement therapy (ERT) with recombinant idursulfase is the main treatment available to decrease morbidity and improve quality of life. However, infusion-associated reactions (IARs) are reported and may limit access to treatment. When premedication or infusion rate reductions are ineffective for preventing IARs, desensitization can be applied. To date, only two MPS II patients are reported to have undergone desensitization. We report a pediatric patient with recurrent IARs during infusion successfully managed with gradual desensitization. Our protocol started at 50% of the standard dosage infused at concentrations from 0.0006 to 0.06 mg/ml on weeks 1 and 2, followed by 75% of the standard dosage infused at concentrations from 0.0009 to 0.09 mg/ml on weeks 3 and 4, and full standard dosage thereafter, infused at progressively increasing concentrations until the standard infusion conditions were reached at 3 months. Our experience can be used in the management of MPS II patients presenting IARs to idursulfase infusion, even when general preventive measures are already administered
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Management of patients with phenylketonuria (PKU) under enzyme replacement therapy: An Italian model (expert opinion)
Full text linkObjective: Phenylketonuria (PKU) is a metabolic disorder necessitating lifelong management to prevent severe neurological impairments. This paper synthesises clinical practices from Italian specialist centres to delineate a unified approach for administering pegvaliase, a novel enzyme replacement therapy for PKU. Methods: Virtual meetings convened in September 2022, gathering a steering committee (SC) of experts from five Italian centres specialising in PKU. The SC reviewed, and discussed clinical practices, and formulated recommendations for pegvaliase treatment. Results: The SC outlined a comprehensive treatment roadmap for PKU management with pegvaliase, emphasising the importance of multidisciplinary care teams, patient selection, pre-treatment evaluation, and education. Recommendations include initial hospital-based pegvaliase administration, regular monitoring of phenylalanine and tyrosine levels, dietary adjustments, and management of adverse events. A consensus was reached on the need for a digital database to manage treatment plans and enhance communication between healthcare professionals and patients. Conclusion: The expert panel's consensus highlights the complexity of PKU management and the necessity for a coordinated, patient-centred approach. The recommendations aim to standardise care across Italian centres and provide a framework for integrating pegvaliase therapy into clinical practice, potentially informing international guidelines. Further research is warranted to evaluate the long-term impact of these practices on patient outcomes and quality of life
Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU)
Full text linkEffect of enzyme substitution therapy on brain magnetic resonance imaging and cognition in adults with phenylketonuria: A case series of three patients
Full text linkPhenylketonuria, the most common inherited metabolic disease, results from a deficiency of phenylalanine hydroxylase enzyme activity that causes high blood phenylalanine levels. Most adults do not adhere to the gold standard therapy: lifelong treatment with a low-phenylalanine diet. Elevated and fluctuating phenylalanine levels in untreated adults can cause white matter abnormalities, neurological symptoms, and cognitive dysfunction (executive function). Pegvaliase, a derivative of the phenylalanine ammonia-lyase enzyme, metabolizes phenylalanine to trans-cinnamic acid and ammonia, and is approved by the US Food and Drug Administration and European Medicines Agency for subcutaneous administration in adults with phenylketonuria and blood phenylalanine concentrations > 600 μmol/L. In clinical trials, it reduced blood phenylalanine, even in patients consuming an unrestricted diet. We report longitudinal results on the first three such adults, in whom phenylalanine levels were quantified monthly, starting 1 year before pegvaliase administration and continuing through achievement of a pegvaliase response (defined as six consecutive monthly blood phenylalanine concentrations < 360 μmol/L while consuming an unrestricted diet). Brain magnetic resonance imaging (MRI) and neuropsychological assessments were performed before starting therapy and after response was achieved. Our results show that all three patients had significantly reduced white matter hyperintensities on brain MRI and improved executive function on neuropsychological assessment, especially on the Paced Auditory Serial Addition Test, which is known to be very sensitive to white matter functioning. To the best of our knowledge, this is the first report of concomitant improvements in cognitive performance and white matter damage after a pharmacological intervention to normalize phenylalanine levels in adults with phenylketonuria consuming an unrestricted diet
The Impact of a Slow-Release Large Neutral Amino Acids Supplement on Treatment Adherence in Adult Patients with Phenylketonuria
Full text linkThe gold standard treatment for phenylketonuria (PKU) is a lifelong low-phenylalanine (Phe) diet supplemented with Phe-free protein substitutes. Adherence to therapy becomes difficult after childhood. Supplementing with large neutral amino acids (LNAAs) has been proposed as an alternative medication to Phe-free protein substitutes (i.e., amino acid mixtures). The aim of this study was to evaluate adherence to therapy and quality of life (QoL) in a cohort of sub-optimally controlled adult PKU patients treated with a new LNAA formulation. Twelve patients were enrolled in a 12-month-trial of slow-release LNAAs (1g/kg/day) plus a Phe-restricted diet. Medication adherence was measured with the Morisky Green Levine Medication Adherence Scale; the QoL was measured using the phenylketonuria-quality of life (PKU-QoL) questionnaire. Phe, tyrosine (Tyr) levels, and Phe/Tyr ratios were measured fortnightly. Before treatment, 3/12 patients self-reported a ‘medium’ adherence to medication and 9/12 r..
Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
Full text linkGaucher Disease Type 3 (GD3) is a rare lysosomal storage disorder characterized by both visceral and neurological involvement. Pulmonary manifestations can significantly impact prognosis and quality of life. This case report highlights the challenges in managing severe pulmonary involvement in GD and explores novel treatment approaches. We present a case of a patient with GD3, diagnosed through neonatal screening, who developed severe lung disease despite early initiation of enzyme replacement therapy (ERT). The patient, carrying compound heterozygous variants in the GBA1 gene (p.Leu483Pro, [p.His294Gln + p.Asp448His]), experienced respiratory distress requiring oxygen therapy from the age of 4 months. High-resolution computed tomography revealed a typical interstitial lung disease pattern. Despite ERT and a marked reduction in storage biomarkers, pulmonary symptoms persisted, accompanied by elevated inflammatory markers. We implemented a treatment regimen of systemic corticosteroids followed by hydroxychloroquine, resulting in clinical improvement. Furthermore, we observed a decrease in inflammatory biomarkers, such as TNF-alpha and Pp38 MAPK levels, providing insights into possible pathogenic mechanisms. This case underscores the limitations of ERT in addressing pulmonary manifestations of GD and highlights the need for personalized treatment strategies. It also emphasizes the importance of further research into the pathogenesis of pulmonary damage in Gaucher disease to develop more effective therapies for these challenging cases. The positive response to anti-inflammatory and immunomodulatory therapies suggests a potential role for these approaches in managing GD-related lung disease
The management of transitional care of patients affected by phenylketonuria in Italy: Review and expert opinion
Full text linkPhenylketonuria (PKU) is a metabolic inherited disorder in which transition from infancy to adult care is particularly difficult and not sufficiently regulated. According to the scientific literature, only few medical centers offer healthcare assistance for adult patients with PKU that are therefore still treated in pediatric settings. This generates psychological, emotional, and organizational discomfort among patients, leading them to discontinue the follow-up. European guidelines and national consensus documents underline this unmet need and the lack of practical recommendations for a structured transitional pathway in PKU. The aim of this review and expert opinion is to propose good practices for managing the transition period of PKU patients, based on the literature and the experience of a panel of Italian experts in PKU. The consensus of the experts was obtained through the administration of three rounds of surveys and one structured interview. The result is the first proposal of a pathway for an efficient transition of PKU patients. Key steps of the proposed pathway are the "a priori" planning involving the pediatric and adult teams, the acceptance of the patient and his/her family to the process, the preliminary defi-nition of appropriate spaces in the structure, the organization of meetings with the joint team, and the appointment of a transition coordinator. For the first time, the involvement of decision makers and patient associations is proposed.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)
- …
