Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

Pompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents with (progressive) muscle weakness and can hence be categorized as a lysosomal storage disorder, a glycogen storage disorder and also a neuromuscular disorder. Pompe disease was the first neuromuscular disorder for which treatment became available, and the development of enzyme replacement therapy for Pompe disease has played a fundamental role in the development of therapies for other rare diseases including neuromuscular and lysosomal storage disorders. This introductory chapter reviews the history, pathophysiology and clinical characteristics of Pompe disease and provides an overview on the effects of enzyme replacement therapy

Symmetries and Lie algebra of the differential-difference Kadomstev-Petviashvili hierarchy

By introducing suitable non-isospectral flows we construct two sets of symmetries for the isospectral differential-difference Kadomstev-Petviashvili hierarchy. The symmetries form an infinite dimensional Lie algebra.Comment: 9 page

Nonlinear Evolution Equations Invariant Under Schroedinger Group in three-dimensional Space-time

A classification of all possible realizations of the Galilei, Galilei-similitude and Schroedinger Lie algebras in three-dimensional space-time in terms of vector fields under the action of the group of local diffeomorphisms of the space \R^3\times\C is presented. Using this result a variety of general second order evolution equations invariant under the corresponding groups are constructed and their physical significance are discussed

Disseminated Fusarium oxysporum Infection in Hemophagocytic Lymphohistiocytosis

Abstract : The portal of entry of disseminated Fusarium spp. infections is still not clearly defined. We report on a disseminated Fusarium oxysporum infection occurring during a long period of severe neutropenia in a child with hemophagocytic lymphohistiocytosis. A nasogastric feeding tube was the possible source of entry of the fungu

Group-invariant solutions of a nonlinear acoustics model

Based on a recent classification of subalgebras of the symmetry algebra of the Zabolotskaya-Khokhlov equation, all similarity reductions of this equation into ordinary differential equations are obtained. Large classes of group-invariant solutions of the equation are also determined, and some properties of the reduced equations and exact solutions are discussed.Comment: 14 page

Variable coefficient nonlinear Schr\"odinger equations with four-dimensional symmetry groups and analysis of their solutions

Analytical solutions of variable coefficient nonlinear Schr\"odinger equations having four-dimensional symmetry groups which are in fact the next closest to the integrable ones occurring only when the Lie symmetry group is five-dimensional are obtained using two different tools. The first tool is to use one dimensional subgroups of the full symmetry group to generate solutions from those of the reduced ODEs (Ordinary Differential Equations), namely group invariant solutions. The other is by truncation in their Painlev\'e expansions

Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation—A 10-Year Single-Center Experience

Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children’s Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration

Quality of life and participation in daily life of adults with Pompe disease receiving enzyme replacement therapy: 10 years of international follow-up

Background: Pompe disease is an inheritable metabolic disorder for which enzyme replacement therapy (ERT) has been available since 2006. Effects of ERT have been shown on distance walked, pulmonary function and survival. We investigated whether it also improves quality of life and participation in daily life in adult patients with the disease. Methods: In an international survey, we assessed quality of life (Short Form 36, SF-36) and participation (Rotterdam Handicap Scale, RHS) annually between 2002 and 2012. Repeated measurements mixed effects models were used to describe the data over time. Results: Responses were available for 174 adult patients. In the periods before and after start of ERT, the median follow-up times were 4 years each (range 0.5-8). The SF-36 Physical Component Summary measure (PCS) deteriorated before ERT (-0.73 score points per year (sp/y); CI 95 % -1.07 to -0.39), while it improved in the first 2 years of ERT (1.49 sp/y; CI 0.76 to 2.21), and remained stable thereafter. The Mental Component Summary measure (MCS) remained stable before and during ERT. After declining beforehand (-0.49 sp/year; CI -0.64 to-0.34), the RHS stabilized under ERT. Conclusion: In adult patients with Pompe disease, ERT positively affects quality of life and participation in daily life. Our results reinforce previous findings regarding the effect of ERT on muscle strength, pulmonary function and survival

Impact of enzyme replacement therapy on survival in adults with Pompe disease: Results from a prospective international observational study

Background: Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survival of adult patients are currently available. The aim of this study was to assess the effect of ERT on survival in adult patients with Pompe disease. Methods. Data were collected as part of an international observational study conducted between 2002 and 2011, in which patients were followed on an annual basis. Time-dependent Cox's proportional hazards models were used for univariable and multivariable analyses. Results: Overall, 283 adult patients with a median age of 48 years (range, 19 to 81 years) were included in the study. Seventy-two percent of patients started ERT at some time during follow-up, and 28% never received ERT. During follow-up (median, 6 years; range, 0.04 to 9 years), 46 patients died, 28 (61%) of whom had never received ERT. After adjustment for age, sex, country of residence, and disease severity (based on wheelchair and ventilator use), ERT was positively associated with survival (hazard ratio, 0.41; 95% CI, 0.19 to 0.87). Conclusion: This prospective study was the first to demonstrate the positive effect of ERT on survival in adults with Pompe disease. Given the relatively recent registration of ERT for Pompe disease, these findings further support its beneficial impact in adult patients