36 Months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy
ABSTRACT Glycogen storage disease type 2(GSD2)/Pompe disease is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span.
We present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 38 adult-onset GSD2 patients (20 female, 18 male) with a mean age at disease onset of 36.2 ± 10.5 years. Mean delay between symptom onset and start of ERT was 14.5 ± 7.2 years. Assessments included serial Walton Gardner Medwin scale, arm function tests, timed 10-meter walk tests, 4- stair climb tests, modified Gowers' maneuvers, 6-minute walk test (6MWT), MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels, and SF-36 selfreporting questionnaires. All tests were performed at baseline and every 12 months for 36 months of ERT.
In the 6MWT we found 21 patients able to walk at baseline a mean distance of 312 ± 165.5 m, improving to 344 ± 165.8 m after 12 months (p=0.006), remaining at 356.4 ± 155.9 m at 24 months (p=0.033), and declining to 325.6 ± 174.8 m after 36 months of ERT (p=0.49, n.s.). The mean FVC in 28 patients was 80.27 ± 14.08% of predicted normal at baseline, after 12 months 79.19 ± 13.09%, at 24 months 78.62 ± 16.55%, and 77.19 ± 18.05%after 36 months. Only mean CK levels were significantly decreased by 8.8% (p=0.041). All other tests were statistically nonsignificant changed.
Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT.
- SourceAvailable from: Christoph M Heyer
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- "The clinical phenotype of LOPD is characterized by slowly progressive proximal muscle weakness involving axial and respiratory muscles that is associated with significant morbidity and reduced life expectancy      .S i n c e 2006, an enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) is available for the treatment of Pompe disease (alglucosidase alfa, Myozyme®, Lumizyme®, Genzyme Corporation , a Sanofi company, Cambridge MA, USA). Clinical studies showed that motor performance, respiratory function and fatigue improved or stabilized in at least two-thirds of LOPD patients who received ERT over 6–36 months        . The functional outcome seems to be best when ERT starts timely, i.e. at an early clinical stage of LOPD  . "
ABSTRACT: Late-onset Pompe disease (LOPD) is a metabolic myopathy caused by mutations in GAA and characterized by proximal muscle weakness and respiratory insufficiency. There is evidence from clinical studies that enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase improves motor performance and respiratory function in LOPD.06/2015; 3. DOI:10.1016/j.ymgmr.2015.03.010
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- "aspx; Bembi et al. 2008). In adult patients, observations regarding the nutritional status only included changes of body mass index under ERT (van der Beek et al. 2009; Ravaglia et al. 2010a; Ravaglia et al. 2010b; Kobayashi et al. 2010; Papdimas et al. 2010; Bernstein et al. 2010; Regnery et al. 2012; Sch€ uller et al. 2012). Recent reports on small cohorts addressed the issue of gastrointestinal symptoms in adults with Pompe disease as well as symptoms such as chronic diarrhoea, bowel urge incontinence, meteorism, gastrointestinal reflux, and obstipation (Bernstein et al. 2010; Sacconi et al. 2010; Remiche et al. 2012). "
ABSTRACT: Objective: To determine the frequency and impact of gastrointestinal symptoms, and bowel and urinary incontinence, as this is currently unknown in adults with Pompe disease. Methods: Adult German Pompe patients and age- and gender-matched controls were asked about symptoms in the upper and lower intestinal tract as well as urinary incontinence using the Gastrointestinal Symptoms Questionnaire and the International Consultation on Incontinence Questionnaires for Bowel Symptoms and Urinary Incontinence. Results: The overall response rate was 78%; 57 patients and 57 controls participated. The mean age of the patients was 48.3 years ±14.7 (28 female, 29 male). 84% of patients were receiving enzyme replacement therapy. Stool urgency, diarrhoea, and urinary urge incontinence were reported significantly more frequently in patients compared to the age- and gender-matched controls (55%, 56%, 33% vs. 20%, 18%, 7%). 20% of Pompe patients used loperamide daily against diarrhoea. No other gastrointestinal tract-related symptoms were reported to occur more frequently in Pompe patients than in controls. Conclusions: Compared to age- and gender-matched controls, both urinary and bowel incontinence occur in a higher frequency in adults with Pompe disease and have a major impact on daily life.
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- "No clear correlation between antibody titers and clinical outcome has so far been demonstrated [Patel et al. 2012]. However, Regnery and colleagues reported an important AE in the case of an adult female patient who developed very high antibody titers (up to 1:819,000), and subsequently presented a worsening of motor function requiring the discontinuation of ERT [Regnery et al. 2012]. "
ABSTRACT: The world of metabolic myopathies has been dramatically modified by the advent of enzyme replacement therapy (ERT), the first causative treatment for glycogenosis type II (GSDII) or Pompe disease, which has given new impetus to research into that disease and also other pathologies. This article reviews new advances in the treatment of GSDII, the consensus about ERT, and its limitations. In addition, the most recent knowledge regarding the pathophysiology, phenotype, and genotype of the disease is discussed. Pharmacological, immunotherapy, nutritional, and physical/rehabilitative treatments for late-onset Pompe disease and other metabolic myopathies are covered, including treatments for defects in glycogen metabolism, such as glycogenosis type V (McArdle disease), and glycogenosis type III (debrancher enzyme deficiency), and defects in lipid metabolism, such as carnitine palmitoyltransferase II deficiency and electron transferring flavoprotein dehydrogenase deficiency, or riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.Therapeutic Advances in Neurological Disorders 09/2013; 6(5):311-21. DOI:10.1177/1756285613487570