Enzyme Replacement Therapy in Lysosomal Storage Diseases

  • Vassili ValayannopoulosEmail author
Part of the Advances in Predictive, Preventive and Personalised Medicine book series (APPPM, volume 6)


Lysosomal storage disorders are inherited metabolic disorders resulting from progressive accumulation of non-recycled compounds that build-up in the lysosomes before expanding to most of body tissues and organs. Impaired enzyme activity, molecular trafficking and transport of these proteins resulting from genetic mutations constitute the main pathogenic mechanisms. Clinical manifestations include storage signs and symptoms such as enlarged liver and spleen, coarse features, skeletal deformities and many of them are associated with a neurodegenerative course. Clinical suspicion can be supported by detection of accumulation of abnormal compounds such as mucopolysaccharides, oligosaccharides, sialic acid and free cholesterol in body fluids and tissues, confirmed by enzymatic assays and molecular testing allowing also prenatal diagnosis and genetic counseling. Management of lysosomal storage disorders can be symptomatic but also specific for some of them with two main treatment modalities: hematopoietic stem cell transplantation and enzyme replacement therapy. Despite recent progress in the field, access of these therapies to key organs such as the brain and bone remain challenging and may be addressed in the near future by original or complementary approaches including molecular chaperones, substrate inhibitors and gene therapy. From this perspective, medical awareness and early detection constitute the cornerstones for early intervention and hope for a better outcome.


Lysosomal storage disease Enzyme replacement therapy Mucopolysaccharidosis type I Mucopolysaccharidosis type II Mucopolysaccharidosis type VI Gaucher disease Pompe disease Fabry disease Personalized medicine 



(recombinant) a-glucosidase


Central nervous system


Cross-reactive immunological material


Enzyme replacement therapy


Forced vital capacity




Glycogen storage disease


Hematopoietic stem-cell transplantation




Infusion-associated reaction


Lysosomal storage disease




Magnetic resonance imaging




  1. 1.
    Boelens JJ (2006) Trends in haematopoietic cell transplantation for inborn errors of metabolism. J Inherit Metab Dis 29:413–420PubMedCrossRefGoogle Scholar
  2. 2.
    Piraud M, Boyer S, Mathieu M, Maire I (1993) Diagnosis of mucopolysaccharidoses in a clinically selected population by urinary glycosaminoglycan analysis: a study of 2,000 urine samples. Clin Chim Acta 221:171–181PubMedCrossRefGoogle Scholar
  3. 3.
    Neufeld E, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Sly WS, Childs B, Beaudet al, Valle D, Kinzler KW, Vogelstein B (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, Health Professions Division, New YorkGoogle Scholar
  4. 4.
    McGill JJ, Inwood AC, Coman DJ, Lipke ML, de Lore D, Swiedler SJ, Hopwood JJ (2010) Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age – a sibling control study. Clin Genet 77:492–498PubMedCrossRefGoogle Scholar
  5. 5.
    Wang RY, Cambray-Forker EJ, Ohanian K, Karlin DS, Covault KK, Schwartz PH, Abdenur JE (2009) Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II. Mol Genet Metab 98:406–411PubMedCrossRefGoogle Scholar
  6. 6.
    Gabrielli O, Clarke LA, Bruni S, Coppa GV (2010) Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up. Pediatrics 125:e183–e187PubMedCrossRefGoogle Scholar
  7. 7.
    Tylki-Szymanska A, Jurecka A, Zuber Z, Rozdzynska A, Marucha J, Czartoryska B (2012) Enzyme replacement therapy for mucopolysaccharidosis II from 3 months of age: a 3-year follow-up. Acta Paediatr 101:e42–e47PubMedCrossRefGoogle Scholar
  8. 8.
    Prasad VK, Kurtzberg J (2010) Transplant outcomes in mucopolysaccharidoses. Semin Hematol 47:59–69PubMedCrossRefGoogle Scholar
  9. 9.
    Peters C, Balthazor M, Shapiro EG, King RJ, Kollman C, Hegland JD, Henslee-Downey J, Trigg ME, Cowan MJ, Sanders J, Bunin N, Weinstein H, Lenarsky C, Falk P, Harris R, Bowen T, Williams TE, Grayson GH, Warkentin P, Sender L, Cool VA, Crittenden M, Packman S, Kaplan P, Lockman LA, Anderson J, Krivit W, Dusenbery K, Wagner J (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894–4902PubMedGoogle Scholar
  10. 10.
    Peters C, Shapiro EG, Anderson J, Henslee-Downey PJ, Klemperer MR, Cowan MJ, Saunders EF, deAlarcon PA, Twist C, Nachman JB, Hale GA, Harris RE, Rozans MK, Kurtzberg J, Grayson GH, Williams TE, Lenarsky C, Wagner JE, Krivit W (1998) Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children The Storage Disease Collaborative Study Group. Blood 91:2601–2608PubMedGoogle Scholar
  11. 11.
    Khanna G, Van Heest AE, Agel J, Bjoraker K, Grewal S, Abel S, Krivit W, Peters C, Orchard PJ (2007) Analysis of factors affecting development of carpal tunnel syndrome in patients with Hurler syndrome after hematopoietic cell transplantation. Bone Marrow Transplant 39:331–334PubMedCrossRefGoogle Scholar
  12. 12.
    Walker RW, Darowski M, Morris P, Wraith JE (1994) Anaesthesia and mucopolysaccharidoses. A review of airway problems in children. Anaesthesia 49:1078–1084PubMedCrossRefGoogle Scholar
  13. 13.
    Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I (2009) Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 123:19–29PubMedCrossRefGoogle Scholar
  14. 14.
    Valayannopoulos V, Nicely H, Harmatz P, Turbeville S (2010) Mucopolysaccharidosis VI. Orphanet J Rare Dis 5:5PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Giugliani R, Rojas VM, Martins AM, Valadares ER, Clarke JTR, Góes JEC, Kakkis ED, Worden MA, Sidman M, Cox GF (2009) A dose-optimization trial of laronidase (Aldurazyme) in patients with mucopolysaccharidosis I. Mol Genet Metab 96:13–19PubMedCrossRefGoogle Scholar
  16. 16.
    Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF (2009) Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 123:229–240PubMedCrossRefGoogle Scholar
  17. 17.
    Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, Izykowski B, Phillips J, Doroshow R, Walot I, Hoft R, Neufeld EF (2001) Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 344:182–188PubMedCrossRefGoogle Scholar
  18. 18.
    Wraith JE, Beck M, Lane R, van der Ploeg A, Shapiro E, Xue Y, Kakkis ED, Guffon N (2007) Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics 120:e37–e46PubMedCrossRefGoogle Scholar
  19. 19.
    Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF (2004) Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 144:581–588PubMedCrossRefGoogle Scholar
  20. 20.
    Pastores GM, Arn P, Beck M, Clarke JTR, Guffon N, Kaplan P, Muenzer J, Norato DYJ, Shapiro E, Thomas J, Viskochil D, Wraith JE (2007) The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. Mol Genet Metab 91:37–47PubMedCrossRefGoogle Scholar
  21. 21.
    Dickson P, McEntee M, Vogler C, Le S, Levy B, Peinovich M, Hanson S, Passage M, Kakkis E (2007) Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol Genet Metab 91:61–68PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Wendt S, Puga AC, Puga A, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Conway AM, Kimura A (2006) A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 8:465–473PubMedCrossRefGoogle Scholar
  23. 23.
    Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A (2007) A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab 90:329–337PubMedCrossRefGoogle Scholar
  24. 24.
    Muenzer J, Beck M, Eng CM, Escolar ML, Giugliani R, Guffon NH, Harmatz P, Kamin W, Kampmann C, Koseoglu ST, Link B, Martin RA, Molter DW, Muñoz Rojas MV, Ogilvie JW, Parini R, Ramaswami U, Scarpa M, Schwartz IV, Wood RE, Wraith E (2009) Multidisciplinary management of Hunter syndrome. Pediatrics 124:e1228–e1239PubMedCrossRefGoogle Scholar
  25. 25.
    Muenzer J, Beck M, Eng CM, Giugliani R, Harmatz P, Martin R, Ramaswami U, Vellodi A, Wraith JE, Cleary M, Gucsavas-Calikoglu M, Puga AC, Shinawi M, Ulbrich B, Vijayaraghavan S, Wendt S, Conway AM, Rossi A, Whiteman DAH, Kimura A (2011) Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Genet Med 13:95–101PubMedCrossRefGoogle Scholar
  26. 26.
    Okuyama T, Tanaka A, Suzuki Y, Ida H, Tanaka T, Cox GF, Eto Y, Orii T (2010) Japan Elaprase Treatment (JET) study: idursulfase enzyme replacement therapy in adult patients with attenuated Hunter syndrome (Mucopolysaccharidosis II, MPS II). Mol Genet Metab 99:18–25PubMedCrossRefGoogle Scholar
  27. 27.
    Wraith JE (2008) Enzyme replacement therapy with idursulfase in patients with mucopolysaccharidosis type II. Acta Paediatr Suppl 97:76–78PubMedCrossRefGoogle Scholar
  28. 28.
    Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J (2008) Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr 167:267–277PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Harmatz P, Whitley CB, Waber L, Pais R, Steiner R, Plecko B, Kaplan P, Simon J, Butensky E, Hopwood JJ (2004) Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). J Pediatr 144:574–580PubMedCrossRefGoogle Scholar
  30. 30.
    Harmatz P, Ketteridge D, Giugliani R, Guffon N, Teles EL, Miranda MCS, Yu Z-F, Swiedler SJ, Hopwood JJ, MPS VI Study Group (2005) Direct comparison of measures of endurance, mobility, and joint function during enzyme-replacement therapy of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): results after 48 weeks in a phase 2 open-label clinical study of recombinant human N-acetylgalactosamine 4-sulfatase. Pediatrics 115:e681–689PubMedCrossRefGoogle Scholar
  31. 31.
    Harmatz P, Kramer WG, Hopwood JJ, Simon J, Butensky E, Swiedler SJ, Mucopolysaccharidosis VI Study Group (2005) Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): a phase I/II study. Acta Paediatr Suppl 94:61–68; discussion 57PubMedCrossRefGoogle Scholar
  32. 32.
    Harmatz P, Giugliani R, Schwartz I, Guffon N, Teles EL, Miranda MCS, Wraith JE, Beck M, Arash L, Scarpa M, Yu Z-F, Wittes J, Berger KI, Newman MS, Lowe AM, Kakkis E, Swiedler SJ, MPS VI Phase 3 Study Group (2006) Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr 148:533–539PubMedCrossRefGoogle Scholar
  33. 33.
    Harmatz P, Giugliani R, Schwartz IVD, Guffon N, Teles EL, Miranda MCS, Wraith JE, Beck M, Arash L, Scarpa M, Ketteridge D, Hopwood JJ, Plecko B, Steiner R, Whitley CB, Kaplan P, Yu Z-F, Swiedler SJ, Decker C, MPS VI Study Group (2008) Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase. Mol Genet Metab 94:469–475PubMedCrossRefGoogle Scholar
  34. 34.
    Harmatz P, Yu Z-F, Giugliani R, Schwartz IVD, Guffon N, Teles EL, Miranda MCS, Wraith JE, Beck M, Arash L, Scarpa M, Ketteridge D, Hopwood JJ, Plecko B, Steiner R, Whitley CB, Kaplan P, Swiedler SJ, Hardy K, Berger KI, Decker C (2010) Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. J Inherit Metab Dis 33:51–60PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Decker C, Yu Z-F, Giugliani R, Schwartz IVD, Guffon N, Teles EL, Miranda MCS, Wraith JE, Beck M, Arash L, Scarpa M, Ketteridge D, Hopwood JJ, Plecko B, Steiner R, Whitley CB, Kaplan P, Swiedler SJ, Conrad S, Harmatz P (2010) Enzyme replacement therapy for mucopolysaccharidosis VI: growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. J Pediatr Rehabil Med 3:89–100PubMedCentralPubMedGoogle Scholar
  36. 36.
    Giugliani R, Harmatz P, Wraith JE (2007) Management guidelines for mucopolysaccharidosis VI. Pediatrics 120:405–418PubMedCrossRefGoogle Scholar
  37. 37.
    Erikson A, Bembi B, Schiffmann R (1997) Neuronopathic forms of Gaucher’s disease. Baillieres Clin Haematol 10:711–723PubMedCrossRefGoogle Scholar
  38. 38.
    Hruska KS, LaMarca ME, Scott CR, Sidransky E (2008) Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat 29:567–583PubMedCrossRefGoogle Scholar
  39. 39.
    Martins AM, Valadares ER, Porta G, Coelho J, Semionato Filho J, Pianovski MAD, Kerstenetzky MS, de Montoril MFP, Aranda PC, Pires RF, Mota RMV, Bortolheiro TC, Brazilian Study Group on Gaucher Disease and other Lysosomal Storage Diseases (2009) Recommendations on diagnosis, treatment, and monitoring for Gaucher disease. J Pediatr 155:S10–18PubMedCrossRefGoogle Scholar
  40. 40.
    Vellodi A, Tylki-Szymanska A, Davies EH, Kolodny E, Bembi B, Collin-Histed T, Mengel E, Erikson A, Schiffmann R, European Working Group on Gaucher Disease (2009) Management of neuronopathic Gaucher disease: revised recommendations. J Inherit Metab Dis 32:660–664PubMedCrossRefGoogle Scholar
  41. 41.
    Schiffmann R, Fitzgibbon EJ, Harris C, DeVile C, Davies EH, Abel L, van Schaik IN, Benko W, Timmons M, Ries M, Vellodi A (2008) Randomized, controlled trial of miglustat in Gaucher’s disease type 3. Ann Neurol 64:514–522PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    van Dussen L, Zimran A, Akkerman EM, Aerts JMFG, Petakov M, Elstein D, Rosenbaum H, Aviezer D, Brill-Almon E, Chertkoff R, Maas M, Hollak CEM (2013) Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease. Blood Cells Mol Dis 50:206–211PubMedCrossRefGoogle Scholar
  43. 43.
    Gonzalez DE, Turkia HB, Lukina EA, Kisinovsky I, Dridi M-FB, Elstein D, Zahrieh D, Crombez E, Bhirangi K, Barton NW, Zimran A (2013) Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: results from a randomized, double-blind, multinational, Phase 3 study. Am J Hematol 88:166–171PubMedCrossRefGoogle Scholar
  44. 44.
    Clavelou P, Besson G, Elziere C, Ferrier A, Pinard J-M, Hermier M, Artigou JY, Germain DP (2006) Neurological aspects of Fabry’s disease. Rev Neurol (Paris) 162:569–580CrossRefGoogle Scholar
  45. 45.
    Moore DF, Kaneski CR, Askari H, Schiffmann R (2007) The cerebral vasculopathy of Fabry disease. J Neurol Sci 257:258–263PubMedCrossRefGoogle Scholar
  46. 46.
    Schaefer RM, Tylki-Szymańska A, Hilz MJ (2009) Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 69:2179–2205PubMedCrossRefGoogle Scholar
  47. 47.
    Moore DF, Altarescu G, Ling GSF, Jeffries N, Frei KP, Weibel T, Charria-Ortiz G, Ferri R, Arai AE, Brady RO, Schiffmann R (2002) Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 33:525–531PubMedCrossRefGoogle Scholar
  48. 48.
    Hirschhorn R, Reuser AJ (2001) Glycogen storage disease type II; acid-glucosidase (acid maltase) deficiency. In: Scriver CR, Sly WS, Childs B, Beaudet al, Valle D, Kinzler KW, Vogelstein B (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, Health Professions Division, New YorkGoogle Scholar
  49. 49.
    ACMG Work Group on Management of Pompe Disease, Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, Case L, Crowley JF, Downs S, Howell RR, Kravitz RM, Mackey J, Marsden D, Martins AM, Millington DS, Nicolino M, O’Grady G, Patterson MC, Rapoport DM, Slonim A, Spencer CT, Tifft CJ, Watson MS (2006) Pompe disease diagnosis and management guideline. Genet Med 8:267–288PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Bijvoet AG, Van Hirtum H, Kroos MA, Van de Kamp EH, Schoneveld O, Visser P, Brakenhoff JP, Weggeman M, van Corven EJ, Van der Ploeg AT, Reuser AJ (1999) Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet 8:2145–2153PubMedCrossRefGoogle Scholar
  51. 51.
    Van Hove JL, Yang HW, Wu JY, Brady RO, Chen YT (1996) High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. Proc Natl Acad Sci U S A 93:65–70PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Raben N, Danon M, Gilbert AL, Dwivedi S, Collins B, Thurberg BL, Mattaliano RJ, Nagaraju K, Plotz PH (2003) Enzyme replacement therapy in the mouse model of Pompe disease. Mol Genet Metab 80:159–169PubMedCrossRefGoogle Scholar
  53. 53.
    Raben N, Fukuda T, Gilbert AL, de Jong D, Thurberg BL, Mattaliano RJ, Meikle P, Hopwood JJ, Nagashima K, Nagaraju K, Plotz PH (2005) Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers. Mol Ther 11:48–56PubMedCrossRefGoogle Scholar
  54. 54.
    Hawes ML, Kennedy W, O’Callaghan MW, Thurberg BL (2007) Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. Mol Genet Metab 91:343–351PubMedCrossRefGoogle Scholar
  55. 55.
    Kishnani PS, Nicolino M, Voit T, Rogers RC, Tsai AC-H, Waterson J, Herman GE, Amalfitano A, Thurberg BL, Richards S, Davison M, Corzo D, Chen YT (2006) Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr 149:89–97PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, Vulto AG, Cromme-Dijkhuis A, Weisglas-Kuperus N, Hop W, Van Hirtum H, Van Diggelen OP, Boer M, Kroos MA, Van Doorn PA, Van der Voort E, Sibbles B, Van Corven EJ, Brakenhoff JP, Van Hove J, Smeitink JA, de Jong G, Reuser AJ, Van der Ploeg AT (2004) Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics 113:e448–e457PubMedCrossRefGoogle Scholar
  57. 57.
    Nicolino M, Byrne B, Wraith JE, Leslie N, Mandel H, Freyer DR, Arnold GL, Pivnick EK, Ottinger CJ, Robinson PH, Loo J-CA, Smitka M, Jardine P, Tatò L, Chabrol B, McCandless S, Kimura S, Mehta L, Bali D, Skrinar A, Morgan C, Rangachari L, Corzo D, Kishnani PS (2009) Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med 11:210–219PubMedCrossRefGoogle Scholar
  58. 58.
    Chen L-R, Chen C-A, Chiu S-N, Chien Y-H, Lee N-C, Lin M-T, Hwu W-L, Wang J-K, Wu M-H (2009) Reversal of cardiac dysfunction after enzyme replacement in patients with infantile-onset Pompe disease. J Pediatr 155:271–275.e2PubMedCrossRefGoogle Scholar
  59. 59.
    Strothotte S, Strigl-Pill N, Grunert B, Kornblum C, Eger K, Wessig C, Deschauer M, Breunig F, Glocker FX, Vielhaber S, Brejova A, Hilz M, Reiners K, Müller-Felber W, Mengel E, Spranger M, Schoser B (2010) Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol 257:91–97PubMedCrossRefGoogle Scholar
  60. 60.
    van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, Herson S, Kishnani PS, Laforet P, Lake SL, Lange DJ, Leshner RT, Mayhew JE, Morgan C, Nozaki K, Park DJ, Pestronk A, Rosenbloom B, Skrinar A, van Capelle CI, van der Beek NA, Wasserstein M, Zivkovic SA (2010) A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med 362:1396–1406PubMedCrossRefGoogle Scholar
  61. 61.
    Desnick RJ (2004) Enzyme replacement and enhancement therapies for lysosomal diseases. J Inherit Metab Dis 27:385–410PubMedCrossRefGoogle Scholar
  62. 62.
    Fukuda T, Ahearn M, Roberts A, Mattaliano RJ, Zaal K, Ralston E, Plotz PH, Raben N (2006) Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol Ther 14:831–839PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Cardone M, Porto C, Tarallo A, Vicinanza M, Rossi B, Polishchuk E, Donaudy F, Andria G, De Matteis MA, Parenti G (2008) Abnormal mannose-6-phosphate receptor trafficking impairs recombinant alpha-glucosidase uptake in Pompe disease fibroblasts. Pathogenetics 1:6PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Drost MR, Schaart G, van Dijk P, van Capelle CI, van der Vusse GJ, Delhaas T, van der Ploeg AT, Reuser AJ (2008) Both type 1 and type 2a muscle fibers can respond to enzyme therapy in Pompe disease. Muscle Nerve 37:251–255PubMedCrossRefGoogle Scholar
  65. 65.
    Kishnani PS, Goldenberg PC, DeArmey SL, Heller J, Benjamin D, Young S, Bali D, Smith SA, Li JS, Mandel H, Koeberl D, Rosenberg A, Chen Y-T (2010) Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab 99:26–33PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Sidman RL, Taksir T, Fidler J, Zhao M, Dodge JC, Passini MA, Raben N, Thurberg BL, Cheng SH, Shihabuddin LS (2008) Temporal neuropathologic and behavioral phenotype of 6neo/6neo Pompe disease mice. J Neuropathol Exp Neurol 67:803–818PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    DeRuisseau LR, Fuller DD, Qiu K, DeRuisseau KC, Donnelly WH Jr, Mah C, Reier PJ, Byrne BJ (2009) Neural deficits contribute to respiratory insufficiency in Pompe disease. Proc Natl Acad Sci U S A 106:9419–9424PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Koeberl DD, Kishnani PS (2009) Immunomodulatory gene therapy in lysosomal storage disorders. Curr Gene Ther 9:503–510PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Mendelsohn NJ, Messinger YH, Rosenberg AS, Kishnani PS (2009) Elimination of antibodies to recombinant enzyme in Pompe’s disease. N Engl J Med 360:194–195PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Reference Center for Inherited Metabolic Disease in Children and Adults (MaMEA) and IMAGINE InstituteNecker-Enfants Malades Hospital and Paris Descartes UniversityParis Cedex 15France

Personalised recommendations