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During three previously reported clinical trials of avalglucosidase alfa in patients with Pompe disease, 17 out of 142 participants were considered by the investigators to be appropriate candidates for home infusion. During their respective trials, these participants received a total of 419 avalglucosidase alfa infusions at home under healthcare professional supervision. They were clinically stable with no history of moderate or severe infusion-associated reactions within at least 12 months prior to starting home infusions. As of February 25, 2022, the 15 participants with late-onset Pompe disease (LOPD) had received between 2 and 48 home infusions and the 2 participants with infantile-onset Pompe disease (IOPD) had received 19 and 20 infusions. Adverse events occurred in 8 (53 %) participants with LOPD and neither of the participants with IOPD. Seven participants with LOPD had a total of 15 non-treatment-related, non-serious adverse events. One participant with LOPD experienced infusion-associated reactions of eyelid edema and flushing during the first home infusion; both were non-serious adverse events classified as grade 1 (mild). Home infusion was later resumed for this participant. Among LOPD participants, event rates for home infusions were comparable to those for clinic infusions: overall adverse events (0.028 vs 0.039 participants with events/infusion, respectively) and adverse events classified as infusion-associated reactions (0.003 vs. 0.006, respectively). No medication errors occurred during home infusion. These data suggest that infusion of avalglucosidase alfa at home is feasible and does not compromise safety for patients who have not experienced an infusion-associated reaction during the preceding 12 months of infusions in a clinical setting. Evaluation of real-world experience with avalglucosidase alfa home infusion in countries where it is already approved is ongoing., Competing Interests: Declaration of competing interest Jordi Díaz-Manera reports advisory board participation for Amicus, Audentes, Lupin, Sanofi, and Sarepta; consulting fees from Audentes, Lupin, Sanofi, and Spark Therapeutics; contracted research for Audentes, Boehringer Ingelheim, Sanofi, and Spark Therapeutics; receipt of intellectual property rights/patent holder for Boehringer Ingelheim; and travel expenses from Amicus, Pfizer, and Sanofi. Derralynn Hughes reports advisory board participation for Amicus, Sanofi, and Takeda; consulting fees from Amicus, Sanofi, and Takeda; and honoraria from Amicus, Sanofi, and Takeda. Anthony Béhin reports fees for participation on scientific boards and sponsorship for scientific congress from Sanofi. Françoise Bouhour reports advisory board participation and travel expenses from Sanofi. James Davison reports advisory board participation for Sanofi, Recordati RRD, and Orchard Therapeutics; consulting fees from Bluebird Bio; and served on the speakers' bureau for Sanofi, Recordati RRD, and FYMCA Medical Ltd. Sevim Erdem-Özdamar reports advisory board participation for Sanofi, Pfizer, and Biogen and has received honoraria from CSL Behring, Alexion, and Sanofi. Si Houn Hahn reports advisory board participation for Alexion Pharmaceutical Inc.; contracted research for Sanofi; royalty from UpToDate, is a member of the Seattle Children's Hospital workforce and is serving as temporary CEO of Key Proteo, Inc. He is an inventor of intellectual property that has been licensed to Key Proteo, Inc., is the founder of Key Proteo, Inc., and has ownership equity interests in the company. Kristina An Haack, Olivier Huynh-Ba, Swathi Tammireddy, Nathan Thibault, and Tianyue Zhou are employees of Sanofi and may have stock ownership in Sanofi. Magali Periquet was an employee of Sanofi at the time of manuscript preparation and holds Sanofi stock. Céline Tard reports personal fees and non-financial support from Sanofi-Genzyme, Pfizer, Alnylam, Roche, Biogen, UCB, Argenx, Alexion, LFB; personal fees from Akcea, Ultragenyx, non-financial support from Santhera. Ans T. van der Ploeg reports advisory board participation for Amicus, BioMarin, Sanofi, and Spark Therapeutics; consulting fees from Amicus, BioMarin, Sanofi, and Spark Therapeutics; and contracted research for Amicus, BioMarin, Sanofi, and Spark Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha-glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life., Methods: We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score., Results: Thirty-two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047)., Conclusions: Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Late-onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α-glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long-term treatment results vary. Avalglucosidase alfa demonstrated non-inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa., Methods: Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow-up. Respiratory (forced vital capacity [FVC]) and motor functions (Six-Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values., Results: Twenty-nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: -1 m/year on the 6MWT after the switch versus -63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different., Discussion: At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening., Conclusion: Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: The French Pompe disease registry was created in 2004 for study of the natural course of the disease in patients. It rapidly became a major tool for assessing the long-term efficacy of enzyme replacement therapy (ERT) after the market release of alglucosidase-alfa., Methods: Approximately 10 years after publication of the baseline characteristics of the 126 initial patients of the French Late-Onset Pompe Disease registry, we provide here an update of the clinical and biological features of patients included in this registry., Results: We describe 210 patients followed at 31 hospital-based French neuromuscular or metabolic centers. The median age at inclusion was 48.67 ± 14.91 years. The first symptom was progressive lower limb muscle weakness, either isolated (50%) or associated with respiratory symptoms (18%), at a median age of 38 ± 14.9 years. At inclusion, 64% of the patients were able to walk independently and 14% needed a wheelchair. Positive associations were found between motor function measure, manual motor test, and 6-minute walk test (6MWT) results, and these parameters were inversely associated with the time taken to sit up from a lying position at inclusion. Seventy-two patients had been followed for at least 10 years in the registry. Thirty-three patients remained untreated a median of 12 years after symptom onset. The standard ERT dose was administered for 177 patients., Discussion: This update confirms previous findings for the adult population included in the French Pompe disease registry, but with a lower clinical severity at inclusion, suggesting that this rare disease is now diagnosed earlier; thanks to greater awareness among physicians. The 6MWT remains an important method for assessing motor performance and walking ability. The French Pompe disease registry provides an exhaustive, nationwide overview of Pompe disease and can be used to assess individual and global responses to future treatments., (© 2023 American Academy of Neurology.)

Background and Objectives: Pompe disease is a rare hereditary glycogen storage disorder due to lysosomal acid alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is the only available treatment. Infusion-associated reactions (IAR) are challenging since there are no guidelines for ERT rechallenge after a drug hypersensitivity reaction (DHR) in Pompe disease. The objective of the present study was to describe IAR and their management in late-onset Pompe disease (LOPD) patients in France, and to discuss the various possibilities of ERT rechallenge., Methods: An exhaustive screening of LOPD patients receiving ERT between 2006 and 2020 from the 31-participating hospital-based or reference centers was performed. The patients who had presented at least one hypersensitivity IAR (=DHR) episode were included. Demographic characteristics of the patients, IAR onset and timing, were retrospectively collected from the French Pompe Registry., Results: Fifteen patients among 115 treated LOPD patients in France presented at least 1 IAR; 80.0% were women. Twenty-nine IAR were reported; 18 (62.1%) IAR were Grade I reactions, 10 (34.5%) IAR were Grade II, and 1 (3.4%) IAR was Grade III. IgE-mediated hypersensitivity was found in 2/15 patients (13.3%). The median [IQR] time from ERT introduction to the first IAR was 15.0 months [11.0-24.0]. ERT was safely and effectively re-introduced either with premedication alone, or in combination with either modified regimen or desensitization protocol, in all 9 rechallenged patients; including in patients with IgE-mediated hypersensitivity, in the patient with the Grade III reaction, as well as in patients with very high anti-GAA titer., Discussion: Based on the results herein and previous reports, we discuss premedication and modified regimen for Grade I reactions, and desensitization in Grade II and III reactions. In conclusion, ERT-induced IAR can be safely and effectively managed with a modified regimen or desensitization protocol in LOPD patients., Competing Interests: Declaration of Competing Interest Dr. Tard reports personal fees and non-financial support from Sanofi-Genzyme. The other authors declare no conflict of interest. Dr. Salort-Campana has received from Sanofi Genzyme travel grants and honoraria for teaching courses, lectures in the last five years and has also received honoraria from Amicus for her participation to the Amicus Advisory Board meetings., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Data on interruption of enzyme replacement therapy (ERT) are scarce in late onset Pompe disease. Due to the COVID-19 crisis, eight neuromuscular reference centers in France were obligated to stop the treatment for 31 patients., Methods: We collected the motor and respiratory data from our French registry, before COVID-19 and at treatment restart., Results: In 2.2 months (mean), patients showed a significant deterioration of 37 m (mean) in the 6-min walk test and a loss of 210 ml (mean) of forced vital capacity, without ad integrum restoration after 3 months of ERT restart., Conclusions: This national study based on data from the French Pompe Registry shows that the interruption of ERT, even as short as a few months, worsens Pompe patients' motor and respiratory function., (© 2021 European Academy of Neurology.)

Background: Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease., Methods: We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period., Findings: Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI -0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%])., Interpretation: We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease., Funding: Sanofi Genzyme., Competing Interests: Declaration of interests SA received reimbursement for attending symposia and other expenses. KB has served on advisory boards for Sanofi Genzyme, AskBio, Spark Therapeutics, and Takeda; and received consultant fees from Sanofi Genzyme, Amicus Therapeutics, AskBio, Spark Therapeutics, Takeda and Valerion. Y-HC has received research support, consulting fees, reimbursement for attending symposium and other expenses, and fees for non-continuing medical education or continuing education services from Sanofi Genzyme. PRC has served as a member of the Pompe Registry North American Advisory Board and undertaken contracted research for Amicus, Sanofi Genzyme, Spark, ReveraGen Biopharma, and NS Pharma. She has been a consultant for Roche and Epirium. She has received travel funding from Roche, Spark, and NS Pharma. JWD has received consulting fees from Audentes, Biogen;, Ionis Pharmaceuticals, Cytokinetics, Pfizer, AveXis, Roche/Genentech Pharmaceuticals, AMO Pharmaceuticals, and Sarepta Therapeutics; and has undertaken contracted research for Biogen, Ionis Pharmaceuticals, Cytokinetics, Roche Pharmaceuticals, AveXis, Sanofi- Genzyme, Sarepta Therapeutics, and Scholar Rock. JD-M has served as a consultant or speaker for Sanofi Genzyme, Lupin, Sarepta, and PTC Therapeutics; and received research support from Boehringer Ingelheim and Sanofi Genzyme. MMD has served as a consultant forArgenX, Catalyst, Cello, CSL Behring, EcoR1, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, RMS Medical, Sanofi Genzyme, Shire Takeda, Spark Therapeutics, and UCB Biopharma; and has received grants from Alexion, Alnylam Pharmaceuticals, Amicus, BioMarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL Behring, US Food and Drug Administration/Office of Orphan Products Development, Genentech, GlaxoSmithKline, Grifols, Kezar, Mitsubishi Tanabe Pharma, Muscular Dystrophy Association, US National Institutes of Health (NIH), Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, UCB Biopharma, Viromed/Healixmith, and TMA. SE-O has served on advisory boards for Sanofi Genzyme. OG-A has served on advisory boards for Amicus, BioMarin, Sanofi, and Takeda; served on speaker's bureau for Sanofi and Takeda; received consulting fees from Amicus, BioMarin, Sanofi Genzyme, Shire Human Genetics Therapies, and Takeda; and undertaken contracted research for Amicus, Freeline, Genentech, Protalix, Sangamo, Sanofi, and Takeda. SI has received honoraria from Actelion, Boehringher Ingelheim, Ever Pharma, Merz Pharma, Servier, Takeda, and Teva. PSK has served on advisory boards for Amicus, Baebies, and Sanofi Genzyme; received consulting fees from Amicus, AskBio, Sanofi Genzyme, and Vertex; undertaken contracted research for Amicus, Sanofi Genzyme, and Valerion; received honoraria from Amicus, AskBio, Sanofi Genzyme, and Vertex; received travel expenses from Amicus and Sanofi Genzyme; and has ownership interests in AskBio and Baebies. HK has served on advisory boards for Alexion, Catalyst Pharmaceuticals, PTC therapeutics, and Sanofi Genzyme; and is on the speaker's bureau of Akcea, Catalyst Pharmaceuticals, and Sanofi Genzyme. SL has served on advisory boards and speaker's bureau, received consulting fees, and undertaken contracted research for Sanofi Genzyme. TM has served on advisory boards for Amicus, Biomarin, Idera, Novartis, Sanofi Genzyme, Ultragenyx, and received travel subsidies and honoraria for related activities; has served as a consultant to NuFactor, Sarepta Therapeutics, and Walgreens, and received travel subsidies and honoraria; served on the speaker's bureau for Sanofi Genzyme and Grifols and received travel subsidies and honoraria for these; and received research funding from Alexion, Alnylam, Amicus, Baxter, Bio-Blast, Biogen, Biomarin, CSL Behring, Sanofi Genzyme, Grifols, GlaxoSmithKline, Idera, ISIS Pharmaceuticals, NIH, Novartis, and Ultragenyx. MR has received research support from Amicus; received consulting fees, honoraria, and travel reimbursement from Sanofi Genzyme, BioMarin, and Amicus; has received royalties from NIH; is a member of a speaker's bureau for NIH; and is a member of the Pompe Registry Scientific Advisory Board. BS has served within the last 3 years on advisory boards for Amicus Therapeutics, Audentes Therapeutics, Dyne, Lupin, Nexien, Sanofi Genzyme, Spark, and UCB; undertaken contracted research for Amicus, Greenovation Biopharm, and Sanofi Genzyme; received honoraria from Alexion and Kedrion; and travel expenses from Kedrion and Sanofi Genzyme. VS has received consulting fees from AveXis, Exonics Therapeutic, Roche, Sanofi Genzyme, and Sarepta Therapeutics; received honoraria from Sanofi Genzyme; and undertaken contracted research from Sanofi Genzyme and Ultragenyx. AT has received reimbursement for participation either as a speaker for lectures and symposia or as a Pompe Registry board member from Sanofi Genzyme. ATvdP provided consulting services, participated in advisory board meetings, and received grants for pre-marketing studies and research from industries (eg, Sanofi Genzyme, Biomarin, and Amicus, etc) via agreements between Erasmus MC and the industries. KAH and her spouse, CH, OH-B, JJ, NT, and TZ are employees of Sanofi Genzyme. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite a wide clinical spectrum, the adult form of Pompe disease is the most common one, and represents more than 90% of diagnosed patients in France. Since the marketing of enzyme replacement therapy (alglucosidase alfa, Myozyme), all reports to date in adults demonstrated an improvement of the walking distance, and a trend toward stabilization of respiratory function, but the majority of these studies were less than 5 years of duration. We report here the findings from 158 treated patients included in the French Pompe Registry, who underwent regular clinical assessments based on commonly used standardized tests (6-minute walking test, MFM scale, sitting vital capacity, MIP and MEP). For longitudinal analyses, the linear mixed effects models were used to assess trends in primary endpoints over time under ERT. A two-phase model better described the changes in distance traveled in the 6-minute walk test and MFM. 6MWT showed an initial significant increase (1.4% ± 0.5/year) followed by a progressive decline (-2.3%/year), with a cut-off point at 2.2 years. A similar pattern was observed in total MFM score (6.6% ± 2.3/year followed by a - 1.1%/year decline after 0.5 years). A single-phase decline with a slope of -0.9 ± 0.1%/year (P < .001) was observed for FVC, and MEP remained stable over the all duration of follow-up. This study provides further evidence that ERT improves walking abilities and likely stabilizes respiratory function in adult patients with Pompe disease, with a ceiling effect for the 6MWT in the first 3 years of treatment., (© 2020 SSIEM.)

Pompe disease (PD) is caused by a deficiency of lysosomal acid α-glucosidase resulting from mutations in the GAA gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder (classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the GAA mutations, to establish the disease epidemiology, and to identify potential genotype-phenotype correlations in French late-onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty-six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty-three different mutations were identified in the GAA gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in-frame deletions, and one large deletion. The common c.-32-13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.-32-13T>G mutation had an older mean age at onset than patients non-exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late-onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late-onset PD patients through a nationwide study covering more than 40 years.

Enzyme replacement therapy consistently improves cardiac function in infantile and juvenile onset patients with Pompe disease and cardiomyopathy, but is apparently not effective in preventing rhythm disorders, an emerging cardiac phenotype in long term survivors. In patients with late onset Pompe disease cardiomyopathy is an exceptional finding while heart rhythm disorders seem to be more frequent. We retrospectively identified, among a cohort of 131 French late onset Pompe disease patients, four patients with severe atrio-ventricular blocks requiring pacemaker implantation. These patients had no other risk factors for cardiovascular diseases or cardiomyopathy. In one patient the atrioventricular block was discovered while still asymptomatic. Cardiac conduction defects are relatively rare in late onset Pompe disease and may occur even in absence of cardiac symptoms or EKG abnormalities. However because of the possible life-threatening complications associated with these conduction defects, cardiac follow-up in patients with late onset Pompe disease should include periodical Holter-EKG monitoring., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Pompe disease is a rare autosomal recessive muscle lysosomal glycogenosis, characterised by limb-girdle muscle weakness and frequent respiratory involvement. The French Pompe registry was created in 2004 with the initial aim of studying the natural history of French patients with adult Pompe disease. Since the marketing in 2006 of enzyme replacement therapy (alglucosidase alfa, Myozyme(®)), the French Pompe registry has also been used to prospectively gather the biological and clinical follow-up data of all adult patients currently treated in France. This report describes the main clinical and molecular features, at the time of inclusion in the French registry, of 126 patients followed up in 21 hospital-based neuromuscular or metabolic centres. Sixty-five men and 61 women have been included in the registry. Median age at inclusion was 49 years, and the median age at onset of progressive limb weakness was 35 years. Fifty-five percent of the patients were walking without assistance, 24% were using a stick or a walking frame, and 21% were using a wheelchair. Forty-six percent of the patients needed ventilatory assistance, which was non-invasive in 35% of the cases. When performed, muscle biopsies showed specific features of Pompe disease in less than two-thirds of the cases, confirming the importance of acid alpha-glucosidase enzymatic assessment to establish the diagnosis. Molecular analysis detected the common c.-32-13T>G mutation, in at least one allele, in 90% of patients. The French Pompe registry is so far the largest country-based prospective study of patients with Pompe disease, and further analysis will be performed to study the impact of enzyme replacement therapy on the progression of the disease., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)