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Priya Sunil Kishnani,
Marc Nicolino,
Thomas Voit,
R Curtis Rogers,
Anne Chun-Hui Tsai,
John Waterson,
Gail E Herman,
Andreas Amalfitano,
Beth L Thurberg,
Susan Richards,
Mark Davison,
Deyanira Corzo,
Y T Chen
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ABSTRACT: 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.
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.
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.
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.
Journal of Pediatrics 07/2006; 149(1):89-97. · 4.11 Impact Factor
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ABSTRACT: Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase deficiency) is an autosomal recessive disorder characterized by deficiency of acid alpha-glucosidase resulting in intra-lysosomal accumulation of glycogen and leading to progressive muscle dysfunction. The natural history of infantile-onset Pompe disease is characterized by hypertrophic cardiomyopathy and profound generalized weakness presenting in the first few months of life, with rapid progression and death usually occurring by one year of age. Late-onset Pompe disease is characterized by onset of symptoms after one year of age, less severe or absence of cardiac involvement and slower progression, with symptoms primarily related to progressive dysfunction of skeletal muscles and respiratory muscle involvement. Recent clinical trials of enzyme replacement therapy have begun to allow greater opportunity for potential improvement in motor status, function, and survival than ever before, with hopes of moving toward maximizing physical function for individuals with Pompe disease. Children are living longer with some achieving independent sitting, creeping, and walking-milestones typically never achieved in the untreated natural history of the disorder. With increased survival, clinical management based on an understanding of the pathology and pathokinesiology of motor function gains importance. This article reviews current knowledge regarding the motor system in Pompe disease and provides an overview of physical therapy management of Pompe disease, including management strategies for individuals on enzyme replacement therapy.
Genetics in Medicine 06/2006; 8(5):318-27. · 4.76 Impact Factor
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Journal of Pediatrics 06/2004; 144(5 Suppl):S35-43. · 4.11 Impact Factor
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American Journal of Medical Genetics Part A 03/2004; 124A(4):436-7. · 2.39 Impact Factor
