***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Background Infantile Pompe disease ( glycogen storage disease type 2 ) is a fatal disorder caused by deficiency of acid α-glucosidase . This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle . The disease is characterized by profound hypotonia , poor growth , organomegaly , and cardiomegaly . Severe hypertrophic cardiomyopathy often is present in early infancy , and most patients die of cardiac or respiratory failure in the first year of life . This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy ( ERT ) . Methods Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA ( rhGAA ) for 1 year . Cardiac monitoring included echocardiography , electrocardiograms ( ECGs ) , chest radiographs , and clinical cardiac evaluation at 4 , 8 , 12 , 24 , 36 , and 52 weeks . At 52 weeks , 6 patients were alive . Results Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT , with near normalization of posterior wall thickness , ventricular mass , and ventricular size . Systolic ventricular function was preserved despite rapid changes in ventricular mass and size . Concomitantly , ECGs documented lengthening of the PR interval and decreased ventricular voltages , whereas chest radiographs documented a decreased cardiothoracic ratio . Symptoms of pulmonary congestion were diminished , and survival was improved . Conclusion The cardiovascular system responds quickly and strikingly to ERT with rhGAA , suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells . Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival Deficiency of acid alpha glucosidase ( GAA ) causes Pompe disease , which is usually fatal if onset occurs in infancy . Patients synthesize a non-functional form of GAA or are unable to form native enzyme . Enzyme replacement therapy with recombinant human GAA ( rhGAA ) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients . We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA . Patients were from the clinical setting and from clinical trials of rhGAA , were 6 months of age , were not invasively ventilated , and were treated with IV rhGAA  at a cumulative or total dose of 20 or 40 mg/kg/2 weeks . Outcome measures included survival , invasive ventilator-free survival , cardiac status , gross motor development , development of antibodies to rhGAA , and levels of urinary Glc(4 ) . Following 52 weeks of treatment , 6/11 ( 54.5 % ) CRIM-negative and 1/21 ( 4.8 % ) CRIM-positive patients were deceased or invasively ventilated ( p<0.0001 ) . By age 27.1 months , all CRIM-negative patients and 4/21 ( 19.0 % ) CRIM-positive patients were deceased or invasively ventilated . Cardiac function and gross motor development improved significantly more in the CRIM-positive group . IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group . CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA . The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein Emerging phenotypes in long-term survivors with Pompe disease on st and ard  enzyme replacement therapy ( ERT ) ( alglucosidase alfa 20 mg/kg/2 weeks ) can include patients with worsening motor function . Whether higher doses of ERT improve skeletal function in these patients has not been systematic ally studied . This exploratory , r and omized , open-label , 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa ( 20 mg/kg/week or 40 mg/kg/2 weeks ) in 13 patients with Pompe disease and clinical decline or a lack of improvement on st and ard ERT : late-onset ( n = 4 ) , infantile-onset ( n = 9 ) . Cross-reactive immunologic material assay-negative patients were excluded . Eleven of 13 patients completed the study . Trends for improvement were seen in total gross motor function , but not mobility ; however , 6 ( late-onset , 2 ; infantile-onset , 4 ) of 11 patients ( 55 % ) who met the entry criteria of motor decline ( late-onset , 4 ; infantile-onset , 7 ) showed improvement in motor and /or mobility skills . No between-regimen differences in efficacy emerged . Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline . Both alternative regimens were generally well tolerated . This study was limited by the small sample size , which is not uncommon for small clinical studies of rare diseases . Additionally , the study did not include direct assessment of muscle pathology , which may have identified potential causes of decreased response to ERT . Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline . Controlled studies are needed to clarify the benefits and risks of this strategy Purpose : A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease . Methods : Open-label , multicenter study of IV alglucosidase alfa treatment in 21 infants 3–43 months old ( median 13 months ) with minimal acid α-glucosidase activity and abnormal left ventricular mass index by echocardiography . Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks ( median 120 weeks ) . Survival results were compared with an untreated reference cohort . Results : At study end , 71 % ( 15/21 ) of patients were alive and 44 % ( 7/16 ) of invasive-ventilator free patients remained so . Compared with the untreated reference cohort , alglucosidase alfa  reduced the risk of death by 79 % ( P < 0.001 ) and the risk of invasive ventilation by 58 % ( P = 0.02 ) . Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks ; 62 % ( 13/21 ) achieved new motor milestones . Five patients were walking independently at the end of the study and 86 % ( 18/21 ) gained functional independence skills . Overall , 52 % ( 11/21 ) of patients experienced infusion-associated reactions ; 95 % ( 19/20 ) developed IgG antibodies to recombinant human lysosomal acid α-glucosidase ; no patients withdrew from the study because of safety concerns . Conclusions : In this population of infants with advanced disease , biweekly infusions with alglucosidase alfa  prolonged survival and invasive ventilation-free survival . Treatment also improved indices of cardiomyopathy , motor skills , and functional independence OBJECTIVE To conduct an open-label , multinational , multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase ( rhGAA ) in treatment of infantile-onset Pompe disease . STUDY DESIGN We enrolled 8 infant patients who had Pompe disease with GAA activity < 1 % of normal , cardiomyopathy , and hypotonia . In the 52-week initial phase , rhGAA was infused intravenously at 10 mg/kg weekly ; an extension phase continued survivors ' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks . Safety measurements included adverse events , laboratory tests , and anti-rhGAA antibody titers . Efficacy evaluations included survival , ventilator use , echocardiograms , growth , and motor and cognitive function . RESULT After 52 weeks of treatment , 6 of 8 patients were alive , and 5 patients were free of invasive ventilator support . Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition . Five patients acquired new motor milestones ; 3 patients walked independently . Four patients died after the initial study phase ; the median age at death or treatment withdrawal for all patients was 21.7 months , significantly later than expected for patients who were not treated . Treatment was safe and well tolerated ; no death was drug-related . CONCLUSION rhGAA improved ventilator-free survival , cardiomyopathy , growth , and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase . Due to virtual absence of acid alpha-glucosidase , patients with classical infantile Pompe disease develop progressive cardiomyopathy , skeletal muscle weakness and respiratory insufficiency leading to death in early infancy . We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions . Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits . Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival , left ventricular mass index , motor development as well as histologic and biochemical analysis of muscle biopsies . This therapy was in general well-tolerated . There was an overall improvement in left ventricular mass , cardiac function , skeletal muscle function and histological appearance of skeletal muscle 
    Output:
    
Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy ( low- quality evidence ) .
One small r and omized controlled trial provided no robust evidence for which dosing schedule of alglucosidase alfa was more effective to treat infantile-onset Pompe disease .