Critical clinical situations in adult patients with Mucopolysaccharidoses (MPS)

Abstract

Background: Mucopolysaccharidoses (MPS) are rare, inherited disorders associated with enzyme deficiencies that result in glycosaminoglycan (GAG) accumulation in multiple organ systems. Management of MPS is evolving as patients increasingly survive to adulthood and undergo multiple surgeries throughout their lives. As surgeries in these patients are considered to be high risk, this can result in a range of critical clinical situations in adult patients. Results: We discuss strategies to prepare for and manage critical clinical situations in adult patients with MPS, including supporting the multidisciplinary team, preoperative and airway assessments, surgical preparations, and postoperative care. We also present eight critical clinical cases (age range: 21-38 years) from four leading inherited metabolic disease centres in Europe to highlight challenges and practical solutions to optimise the care of adult patients with MPS. Critical clinical situations included surgical procedures, pregnancy and a thrombus in a port-acath. Conclusions: Individualised strategies to manage critical clinical situations need to be developed for each patient to compensate for the heterogeneous symptoms that may be present and the potential complications that may occur. These strategies should include input from the wider MDT, and be coordinated by metabolic specialists with expertise in the management of MPS disorders and surgery in adult patients with MPS.

The Impact of Excluding Nonrandomized Studies From Systematic Reviews in Rare Diseases: “The Example of Meta-Analyses Evaluating the Efficacy and Safety of Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis”

“…Accordingly, the selection of case reports should be considered in an MPS systematic review if subgroup analyses were planned (Pérez-López et al, 2017;Pérez-López et al, 2018;Sampayo-Cordero et al, 2018). In addition, we observed that some relevant information about treatment management was usually reported in case reports (Lampe et al, 2019b;Stepien et al, 2020), and previous publications has stated the relevance of case reports to propose clinical novelties (Nakamura et al, 2014;Sampayo-Cordero et al, 2020a).…”

“…The randomized trials usually recruit pediatric patients (Wraith et al, 2004;Muenzer et al, 2006). Importantly, the clinical manifestations of MPS in adulthood are different from pediatric patients (Lampe et al, 2019b;Stepien et al, 2020). So, the exclusion of nonrandomized studies prevents the assessment of the efficacy and safety of ERT in adulthood.…”

Otorhinolaryngological Management in Taiwanese Patients with Mucopolysaccharidoses

“…According to Stepien et al 31 , because the standard tools and assessments used by anesthesiologists may not be adequate for the assessment of MPS patients with complex airways, a more thorough assessment involving an ENT consultant should also be carried out preoperatively. In our center, before giving general anesthesia to MPS patients, entire airway evaluation with flexible fiberbronchoscopy is always done beforehand.…”

The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)

“…Additionally, the individualization of therapies and management strategies is a key factor to successfully treat patients with rare diseases. So, new proposals dealing with uncommon situations in the treatment of rare-disease patients have great relevance to translate clinical research into clinical practice [7,8]. One of the aims of systematic reviews on therapeutic interventions is to summarize the state of art in this intervention [12].…”

“…Furthermore, in rare diseases, the phenotype and genotype heterogeneity limit the generalization of the data from clinical trials to clinical practice [1,6]. Thus, pharmacological treatment of patients with orphan and ultra-orphan drugs is more dependent on individualized strategies than treatment of more prevalent diseases [7,8].…”