Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study.

Objective: To determine the effect of enzyme replacement therapy (ERT) after 5 years and to identify predictors for a favorable response because few data are available on the long-term efficacy of ERT in Pompe disease.

Methods: We included 102 adult patients with Pompe disease in a nationwide, prospective cohort study. We assessed muscle strength (manual muscle testing with Medical Research Council [MRC] grading, handheld dynamometry [HHD]), muscle function (6-minute walk test, Quick Motor Function Test), daily life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale), and pulmonary function (forced vital capacity [FVC] in upright and supine positions, maximum inspiratory and expiratory pressures) at 3- to 6-month intervals before and after the start of ERT.

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study.

Background: Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined.

Quantification of Diaphragm Mechanics in Pompe Disease Using Dynamic 3D MRI.

Background: Diaphragm weakness is the main reason for respiratory dysfunction in patients with Pompe disease, a progressive metabolic myopathy affecting respiratory and limb-girdle muscles. Since respiratory failure is the major cause of death among adult patients, early identification of respiratory muscle involvement is necessary to initiate treatment in time and possibly prevent irreversible damage. In this paper we investigate the suitability of dynamic MR imaging in combination with state-of-the-art image analysis methods to assess respiratory muscle weakness.

Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy.

Purpose: To determine the effect of antibodies against recombinant human acid α-glucosidase (rhGAA) on treatment efficacy and safety, and to test whether the GAA genotype is involved in antibody formation.

Methods: We used enzyme-linked immunosorbent assay (ELISA) to determine anti-rhGAA antibody titers at baseline and at 6, 12, and 36 months of rhGAA treatment. We measured the capacity of antibodies to neutralize rhGAA enzymatic activity or cellular uptake and the effects on infusion-associated reactions (IARs), muscle strength, and pulmonary function.

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.

Background: Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury.

Methods And Results: In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease.

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.

Safety and efficacy of exercise training in adults with Pompe disease: evalution of endurance, muscle strength and core stability before and after a 12 week training program.

Background: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy.

Methods: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks.

Lung MRI and impairment of diaphragmatic function in Pompe disease.

Background: Pompe disease is a progressive metabolic myopathy. Involvement of respiratory muscles leads to progressive pulmonary dysfunction, particularly in supine position. Diaphragmatic weakness is considered to be the most important component.

Exercise training in adults with Pompe disease: the effects on pain, fatigue, and functioning.

Objective: To assess if a 12-week exercise intervention to improve aerobic fitness, muscle strength, and core stability also had an impact on fatigue, pain, activity, and participation in adults with Pompe disease, an inherited neuromuscular disorder.

Design: Open-label trial. Change was assessed by the chi-square test and Wilcoxon signed-rank test.

Increased aortic stiffness and blood pressure in non-classic Pompe disease.

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study.

Phenotypical variation within 22 families with Pompe disease.

Background: Pompe disease has a broad clinical spectrum, in which the phenotype is partially explained by the genotype. The aim of this study was to describe phenotypical variation among siblings with non-classic Pompe disease. We hypothesized that siblings and families with the same genotype share more similar phenotypes than the total population of non-classic Pompe patients, and that this might reveal genotype-phenotype correlations.

Remarkably low fibroblast acid α-glucosidase activity in three adults with Pompe disease.

Introduction: Most adults with Pompe disease are compound heterozygotes in which one acid α-glucosidase (GAA) allele harbors the c.-32-13T>G mutation, causing partial loss of GAA, and the other allele harbors a fully deleterious mutation. The fibroblast GAA activity in these patients is usually between 5% and 25% of the average in healthy individuals.

Inflammatory profile of awake function-controlled craniotomy and craniotomy under general anesthesia.

Background: Surgical stress triggers an inflammatory response and releases mediators into human plasma such as interleukins (ILs). Awake craniotomy and craniotomy performed under general anesthesia may be associated with different levels of stress. Our aim was to investigate whether those procedures cause different inflammatory responses.