Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

  • M. PinedaEmail author
  • M. O’Callaghan
  • A. Fernandez Lopez
  • M. J. Coll
  • R. Ullot
  • G. Garcia-Fructuoso
Research Report
Part of the JIMD Reports book series (JIMD, volume 30)


Mucopolysaccharidosis type VI (MPS VI) is a progressive, autosomal, recessive lysosomal disorder. This disorder, due to a deficiency in N-acetylgalactosamine-4-sulfatase (ASB), results in an accumulation of glycosaminoglycan (GAG), causing multiple organ failures. In this study, monochorionic biamniotic twins with the severe form of MPS VI underwent enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (galsulfase) at 1 mg/kg. After 9 years of ERT, a comprehensive clinical examination was performed. Several types of biochemical, immunological, and genetic investigations were also conducted. Both twins showed the typical symptoms and signs of MPS VI at baseline, including short stature, progressive dysmorphic facial features, and dysostosis multiplex. Twin 2 presented stronger multisystemic involvement, with marked musculoskeletal, neurological, and odontological components. She also developed an ischemic spinal cord lesion after surgery, which is the first case described in the literature in Maroteaux–Lamy syndrome. However, the extent of disease was found to be equally stabilized in the two sisters, concretely the cardiac and respiratory functions and body length. The early diagnosis and treatment of MPS VI are critical for an optimal clinical outcome, and further evidence for the new treatment strategies is needed.


Carpal Tunnel Syndrome Enzyme Replacement Therapy Dermatan Sulfate Deep Anterior Lamellar Keratoplasty Spinal Cord Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Scientific editorial assistance was provided by Irantzu Izco-Basurko and Fernando Rico-Villademoros (Cociente S.L.). The authors thank the family for their collaboration.


  1. Azevedo ACMM, Schwartz IV, Kalakun L, Brustolin S, Burin MG, Beheregaray APC, Leistner S, Giugliani C, Rosa M, Barrios P, Marinho D, Esteves P, Valadares E, Boy R, Horovitz D, Mabe P, de Silva LCA, de Souza ICN, Ribeiro M, Martins AM, Palhares D, Kim CA, Giugliani R (2004) Clinical and biochemical study of 28 patients with mucopolysaccharidosis type VI. Clin Genet 66:208–213CrossRefPubMedGoogle Scholar
  2. Baum H, Dogson KS, Spencer B (1959) The assay of arylsulphatases A and B in human urine. Clin Chim Acta 4:453–455CrossRefPubMedGoogle Scholar
  3. Brands MM, Hoogeveen-Westerveld M, Kroos MA, Nobel W, Ruijter GJ, Özkan L, Plug I, Grinberg D, Vilageliu L, Halley DJ, van der Ploeg AT, Reuser AJ (2013) Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase. Orphanet J Rare Dis 8:51CrossRefPubMedPubMedCentralGoogle Scholar
  4. Braunlin E, Rosenfeld H, Kampmann C, Johnson J, Beck M, Giugliani R, Guffon N, Ketteridge D, Sá Miranda CM, Scarpa M, Schwartz IV, Leão Teles E, Wraith JE, Barrios P, Dias da Silva E, Kurio G, Richardson M, Gildengorin G, Hopwood JJ, Imperiale M, Schatz A, Decker C, Harmatz P, MPS VI Study Group (2013) Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy. J Inherit Metab Dis 36(2):385–394CrossRefPubMedGoogle Scholar
  5. Decker C, Yu ZF, Giugliani R, Schwartz IV, Guffon N, Teles EL, Miranda MC, 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 3:89–100PubMedPubMedCentralGoogle Scholar
  6. Fesslova V, Corti P, Sersale G, Rovelli A, Russo P, Mannarino S, Butera G, Parini R (2009) The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses. Cardiol Young 19:170–178CrossRefPubMedGoogle Scholar
  7. Furujo M, Kubo T, Kosuga M, Okuyama T (2011) Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI. Mol Genet Metab 104:597–602CrossRefPubMedGoogle Scholar
  8. Garrido E, Chabás A, Coll MJ, Blanco M, Domínguez C, Grinberg D, Vilageliu L, Cormand B (2007) Identification of the molecular defects in Spanish and Argentinian mucopolysaccharidosis VI (Maroteaux–Lamy syndrome) patients, including 9 novel mutations. Mol Genet Metab 92:122–130CrossRefPubMedGoogle Scholar
  9. Giugliani R, Harmatz P, Wraith JE (2007) Management Guidelines for Mucopolysaccharidosis VI. Pediatrics 120:405–418CrossRefPubMedGoogle Scholar
  10. Giugliani R, Lampe C, Guffon N, Ketteridge D, Leão-Teles E, Wraith JE, Jones SA, Piscia-Nichols C, Lin P, Quartel A, Harmatz P (2014) Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux–Lamy syndrome)–10-year follow-up of patients who previously participated in an MPS VI Survey Study. Am J Med Genet A 164(8):1953–1964CrossRefPubMedCentralGoogle Scholar
  11. Harmatz P, Giugliani R, Schwartz IV, Guffon N, Teles EL, Miranda MC, Wraith JE, Beck M, Arash L, Scarpa M, Ketteridge D, Hopwood JJ, Plecko B, Steiner R, Whitley CB, Kaplan P, Yu ZF, 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(4):469–475Google Scholar
  12. Harmatz P, Yu ZF, Giugliani R, Schwartz IV, Guffon N, Teles EL, Miranda MC, 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(1):51–60CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hendriksz CJ, Giugliani R, Harmatz P, Lampe C, Martins AM, Pastores GM, Steiner RD, Leão Teles E, Valayannopoulos V; CSP Study Group (2013) Design, baseline characteristics, and early findings of the MPS VI (mucopolysaccharidosis VI) Clinical Surveillance Program (CSP). J Inherit Metab Dis 36(2):373–384Google Scholar
  14. Lael GN, de Paula AC, Leone C, Kim CA (2010) Echocardiographic study of paediatric patients with mucopolysaccharidosis. Cardiol Young 20:254–261CrossRefGoogle Scholar
  15. Lampe C, Lampe C, Schwarz M, Müller-Forell W, Harmatz P, Mengel E (2013) Craniocervical decompression in patients with mucopolysaccharidosis VI: development of a scoring system to determine indication and outcome of surgery. J Inherit Metab Dis 36(6):1005–1013CrossRefPubMedGoogle Scholar
  16. Litjens T, Baker EG, Beckmann KR, Morris CP, Hopwood JJ, Callen DF (1989) Chromosomal localization of ARSB, the gene for human Nacetylgalactosamine-4-sulphatase. Hum Genet 82:67–68CrossRefPubMedGoogle Scholar
  17. Maroteaux P, Leveque B, Marie J, Lamy M (1963) A new dysostosis with urinary elimination of chondroitin sulfate B. Presse Med 71:1849–1852PubMedGoogle Scholar
  18. 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 77:492–498CrossRefPubMedGoogle Scholar
  19. Neufeld E, Muenzer J (2001) The mucopolysaccharidoses. In: Valle D, Beaudet A, Vogelstein B, Kinzler K, Antonarakis S, Ballabio A (eds) Scriver’s online metabolic and molecular bases of inherited disease. McGraw-Hill Global Education Holdings, LLC, New York, pp 2465–2494Google Scholar
  20. Panin G, Naia S, Dall'Amico R, Chiandetti L, Zachello F, Catassi C, Felici L, Coppa GV (1986) Simple spectrophotometric quantification of urinary excretion of glycosaminoglycan sulfates. Clin Chem 32(11):2073–2076PubMedGoogle Scholar
  21. Pauchard N, Garin C, Jouve JL, Lascombes P, Journeau P (2014) Perioperative medullary complications in spinal and extra-spinal surgery in mucopolysaccharidosis: a case series of three patients. JIMD Rep 16:95–99Google Scholar
  22. Poorthuis B, Wevers R, Kleijer W, Groener JE, de Jong JG, van Weely S, Niezen-Koning KE, van Diggelen OP (1999) The frequency of lysosomal storage disease in the Netherlands. Hum Genet 105:151–156CrossRefPubMedGoogle Scholar
  23. Scarpa M, Barone R, Fiumara A, Astarita L, Parenti G, Rampazzo A, Sala S, Sorge G, Parini R (2009) Mucopolysaccharidosis VI: the Italian experience. Eur J Pediatr 168:1203–1206CrossRefPubMedGoogle Scholar
  24. Thümler A, Miebach E, Lampe C, Pitz S, Kamin W, Kampmann C, Link B, Mengel E (2012) Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series. J Inherit Metab Dis 35:1071–1079CrossRefPubMedGoogle Scholar
  25. Valayannopoulos V, Nicely H, Harmatz P, Turbeville S (2010) Mucopolysaccharidosis VI. Orphanet J Rare Dis 5:5CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • M. Pineda
    • 1
    Email author
  • M. O’Callaghan
    • 1
  • A. Fernandez Lopez
    • 2
  • M. J. Coll
    • 3
  • R. Ullot
    • 4
  • G. Garcia-Fructuoso
    • 5
  1. 1.Fundación y Servicio de NeuropediatríaHospital Universitario Sant Joan de Déu, CIBERERBarcelonaSpain
  2. 2.Servicio de pediatríaHospital Sant Joan de Déu, Universidad de BarcelonaBarcelonaSpain
  3. 3.Sección Errors CongènitsServei de Bioquímica i Genètica Molecular, Hospital Clinic, CIBERERBarcelonaSpain
  4. 4.Servicio de Traumatología y OrtopediaHospital Universitario Sant Joan de DéuBarcelonaSpain
  5. 5.Servicio de NeurocirugíaHospital Universitario Sant Joan de DéuBarcelonaSpain

Personalised recommendations