Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome
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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.
KeywordsCarpal Tunnel Syndrome Enzyme Replacement Therapy Dermatan Sulfate Deep Anterior Lamellar Keratoplasty Spinal Cord Damage
Scientific editorial assistance was provided by Irantzu Izco-Basurko and Fernando Rico-Villademoros (Cociente S.L.). The authors thank the family for their collaboration.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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