•Updated Study Manager and Medical Monitor titles•Expanded types of data collected from this long-term study•Added urinary oligosaccharides analysis as exploratory objective.•Added cross-reacting immunologic material (CRIM) status and T cells analysis for research purposes only•New citation added that was not available at time original protocol•Study design:Added “multinational” to clarify that study was multinational•Clarified independent data safety monitoring board (DSMB) would review safety information•Subject population and selection:Clarified that only subjects with Pompe disease might participate•Subject withdrawal:Clarified that in this 10-year study, subject might be lost to follow-up before EOS period•"Package insert" was changed to “full prescribing information”•Revised text to indicate that actual infusion schedule was to be determined by investigator•Revised section title to reflect exploratory variables•Updated that non-baseline assessments had window of +/-60 days; immunoglobulin G (IgG collection-Baseline and Months 3,6,9,12,15,18,21,24, annually thereafter;vital signs-monitored at Baseline and at end of each infusion;•Modified Leiter-R scale assessment -not performed at Baseline;•Length, height, weight measurements description were made consistent;•Clarified procedures for CRIM, T cell assays, blood collection,vital signs,infusions•Revised schedule for new T cell assay at Months 1,3,6,9,12,15,18,21,24 only•Table reflected new exploratory assessments.•Vital signs-monitored at end of each infusion at Months 6,12,18,24, annually thereafter•Serum IgG,vital signs assessments were updated to be performed at Month 12 and every 12 months thereafter (or on study withdrawal)•Procedures for urinary oligosaccharides, CRIM and T cell assays were described•Revised details of hearing test procedures•Vital signs-recorded if subject had recurrent IAR•Clarified circumstances to report SAEs to regulatory agencies•Updated definition of Center for Disease Control (CDC).

•Study duration-'over a 10-year period' was added.•Enrollment period was not limited prospectively to allow enrollment of sufficient numbers of subjects.•Study was opened up to allow subjects who had received Myozyme before their first birthday to bolster enrollment. Investigational 2000 Litre Myozyme was provided by Sponsor until approval of this product.•Frequency of efficacy assessments was based on subject’s age or time in study, rather than yearly.•Bayley-III test-measured cognitive language and motor development,each subscale of Bayley-III was assessed until subject reached 42months of age or maximum score for that subscale, if earlier.•Cognition-assessed by Leiter-R concurrently with last administration of Bayley-III cognitive subscale and annually thereafter.•GMFM-66 and Pompe PEDI was performed.•Magnetic resonance imaging (MRI) assessment-performed at discretion of Investigator.•T cell assessment-removed.•Clarified appropriate hearing tests for subjects of various ages.•Added gross motor ability estimator (GMAE) for gross motor function measure (GMFM) scores analysis.•Updated current investigator’s brochure with risks associated with Myozyme use.•Clarified this was a study and not sub-registry program.•Updated definition of “ongoing” in context of AEs continuing at time subject withdrew or study completion.•Concomitant therapies-not recorded.•Vital signs-recorded before and at end of each infusion.•Medical/surgical history-added to allow collection of retrospective AEs.•IgG collection assessment-performed every 3 months and every 12months and urine oligosaccharide assessment-performed every 6months and every 12months, both with delimiters of Study Month specified.•Physical Growth-performed by same individual at each subject visit (as far as possible).•Leiter-R wording revised to emphasize its role as measure of intellectual ability.•Neuroimaging assessments-performed by MRI at discretion of Investigator.•Clarified requirements to follow and report AEs/SAEs.

•Tradename “Myozyme” was replaced globally with nonproprietary name “alglucosidase alfa” that applied regardless of manufacturing scale.•Urine oligosaccharides indicated specific oligomer measured in assay.•GMFM-66 was replaced by GMFM-88.•Updated department name with exception of pharmacovigilancesafety@genzyme.com e-mail address;•Added date of Amendment 3 on title page.•Change in responsible study personnel and to include Medical Monitor signature on cover page to comply with global standards.•Reflected that cap on number of sites that might participate was not needed; •Clarified that subjects must receive their first infusion of Myozyme before 1 year of age to be included in study;•Expanded the pool of eligible subjects;•Emphasize that subjects participated in study were treated with Myozyme commercially outside of protocol, and provided study requirements for investigators who might chosen to implement home infusions to treat subject participating instudy;•Provideddetailed example of when inhibitory antibody testing was clinically indicated.•Allowed acid alpha-glucosidase(GAA) mutation analysis, beyond documentation of diagnosis of Pompe disease based on deficient endogenous GAA activity or GAA mutation analysis, for use in interpreting the outcomes of the study.•Safety information on anaphylaxis and allergic reactions reflected changes in current Myozyme (alglucosidase alfa) label was added.•Added new safety information from the current label.•Highlighted important information on risks.•Subjects received commercial Myozyme during study; hence,pharmacy manual does not apply.•Concomitant therapies were collected along with concomitant medications for duration of study.•Only 4 subtests were administered estimated brief IQ.•Visual screening-clinically significant changes in vision as compared to Baseline results were noted as AEs.•Relevant changes were made within schedule of assessment and its footnotes.•Updated list to include new references.

•Updated department name; •Updated Section 9.1 Schedule of Assessments; •For subjects on home infusion, some assessments might be allowed to be conducted in the home setting and were not required to be conducted in the clinic.

•Updated cover page and protocol synopsis; •Exclusion criteria: clarifiedy that subjects cannot be enrolled in any clinical trial utilizing an investigational therapy as that could interfere with efficacy or safety of Myozyme and skew observational results of the AGLU03606 study. •Treatment administration-Myozyme would be administered at 20 mg/kg body weight as prescribed by the treating physician every 2 weeks as an intravenous infusion. •Serum IgE antibody testing-in the event that subject experienced a moderate, severe, or recurrent IAR, the subject should return to the study centre at least 72 hours after the infusion ends.

• Changed “Global Subject Safety and Risk Management” to “Global Pharmacovigilance and Epidemiology” to reflect recent department name change. • Title Page: Added date of Protocol Amendment 6; •Updated Study Manager, Medical Monitor and Statistician information; • Updated protocol synopsis; •1) Treatments administered was updated with 'If clinically feasible, all subjects would continue at the same dose throughout the study. Any modification to the dose and/or frequency of dosing is not permitted unless it is due to disease progression or to an AE, in which case it is not a protocol deviation, but the Investigator must consult with the Sponsor’s Medical Monitor and Global Safety Officer in the event of a dose change. The dosing change and the reasons for it will be documented on the appropriate CRFs.' 2) •Complement Activation Testing and Serum Tryptase Testing- plasma sample should be drawn within 1 to 3 hours of the event for complement activation testing, when clinically indicated.

•Change to the inclusion/exclusion criteria, •Addition of Leiter-3, •Updated potential risks and potential benefits •Updated product name as 'Myozyme®/Lumizyme® (alglucosidase alfa). •Updated cognitive development with change in Brief IQ score of the Leiter International Performance Scale – Revised (Leiter-R) and/or the change in the Nonverbal IQ score of the Leiter International Performance Scale – 3rd Edition (Leiter-3) (starting at the final assessment of the Bayley-III before 42 months of age). •Updated information within Summary of Potential Risks and Summary of Potential Benefits. •GAA mutation analysis was to be conducted only if written results were not available. •Updated infusion-associated reactions (IAR) definition as AEs that occur during the infusion or within up to 24 hours after the start of infusion and were considered as related or possibly related to the ERT by the Investigator or the Sponsor. •An event occurring >=24 hours after the start of an infusion might be judged an IAR if a delayed reaction was considered possible by Investigator or Sponsor. •Copies of score sheets for cognitive function and motor development assessments would be sent to central Genzyme representative for centralised scoring.