Supportive clinical evidence from sibling studies suggests that early intervention provides multiple opportunities to improve patient outcomes through disease-specific management and early initiation of ERT, if available.1–6
ERT, whether initiated early or later in life, has been shown to improve key clinical parameters, such as endurance and pulmonary measures, which are critical to quality of life, maintenance of ambulation, and activities of daily living.7,8
ERT is currently available in many countries for the treatment of patients with MPS I, II, IVA, and VI.
The new era of management for progressive, complex, genetic conditions, such as mucopolysaccharidosis (MPS) disorders, hinges on the efficient coordination of each patient’s healthcare team.1
Geneticists and/or metabolic specialists are typically at the centre of the medical home and help to coordinate multidisciplinary care and an individualised management plan.2,3
Many MPS disorders have available management guidelines and
speciality-specific consensus recommendations regarding lifelong management of MPS. Guidelines typically recommend the following:2,4
Early and ongoing assessments from a coordinated-care team can improve patient outcomes and may help prevent irreversible damage.4
As an example, the table below represents the suggested schedule of evaluations for patients with Morquio A (MPS IVA).2
Frequency of assessments and involvement of specific specialists vary across the different MPS types. For patients with MPS diseases associated with primary neurodegenerative and cognitive complications, such as MPS I, II, and III, additional and regular neurobehavioural and psychiatric evaluations are recommended.4–6
In addition to speciality-specific assessments that should be done to facilitate positive long-term outcomes for patients with MPS, important steps can be taken by the coordinating physician, typically the geneticist and/or metabolic specialist, related to general health. Their role in educating other healthcare professionals (e.g. dentists, physiotherapists, paediatricians, family doctors) and families about the disease and general management strategies is critical and should include the following2:
Speciality-specific assessments, as well as regular physical examinations and overall health interventions, should follow recommended guidelines, which may vary among MPS subtypes.2
Improvements in the treatment of MPS disorders are contributing to long-term outcomes for patients, necessitating new approaches to lifelong management.
As patients age, some may begin to manage their own healthcare, making physician-guided transition to the adult setting critical.2 Physicians should ensure the following:
The transition from paediatric to adult care and long-term adult care are critical areas to address in care plans for adolescent and adult patients.2 Long-term care considerations are ideally best addressed in a centre with significant MPS experience, and they require careful coordination across specialities.2,8 Long-term issues include but are not limited to:
Long-term management of MPS disorders, including ongoing assessments and a site-specific transition strategy from paediatric to adult care, may lead to sustained improvement in quality of life and a better future for your patients.2,8–10
Because clinical manifestations of mucopolysaccharidosis (MPS) disorders are multisystemic, a patient-specific, multidisciplinary approach is required to proactively recognise and manage complications.1
Patients with MPS disorders typically have a number of surgical interventions over their lifetimes. A natural history study assessing a cohort of 325 patients with Morquio A (MPS IVA) found that over 70% of patients had at least one surgical procedure.2
Patients with MPS have a high perisurgical mortality rate due to multiple factors, including upper and lower airway obstruction, cervical spinal instability, respiratory impairment, cardiovascular morbidities, and frequent infections.2–4 For example, surgical complications resulted in an 11% mortality rate in patients with Morquio A (n=27).5
Creating a surgical plan is crucial and involves a multidisciplinary team of specialists who are, ideally, also experienced in treating patients with MPS.3
Surgical risk assessment and perioperative monitoring are fundamental components of a tailored surgical plan, and they can reduce the risks of negative surgical outcomes and mortality in patients with MPS.3,9,10
References: 1. McGill JJ et al. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age – a sibling control study. Clin Genet. 2010;77(5):492–498. 2. Furujo M et al. Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI. Mol Genet Metab. 2011;104(4):597–602. 3. Clarke LA. Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses: glycosaminoglycan storage is merely the instigator. Rheumatology (Oxford). 2011;50(suppl 5):v13–18. 4. Lehman TJA et al. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41–v48. 5. Morishita K et al. Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v19–v25. 6. Muenzer J, Beck M, Eng CM, et al.Genet Med. 2011;13(2):95–101. doi:10.1097/GIM.0b013e3181fea459. 7. Hendriksz C. Improved diagnostic procedures in attenuated mucopolysaccharidosis. Br J Hosp Med. 2011;72(2):91–95. 8. Muenzer J. Early initiation of enzyme replacement therapy for the mucopolysaccharidoses. Mol Genet Metab. 2014;111(2):63–72. 9. Hendriksz CJ et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. 10. Bagewadi S et al. Home treatment with Elaprase® and Naglazyme® is safe in patients with mucopolysaccharidoses types II and VI, respectively. J Inherit Metab Dis. 2008;31(6):733–737. 11. BioMarin Pharmaceutical Inc. VIMIZIM website. http://www.vimizim.com/. Accessed December 21, 2015. 12. BioMarin Pharmaceutical Inc. NAGLAZYME website. http://www.naglazyme.com/. Accessed December 21, 2015. 13. VIMIZIM [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2014. 14. Wood TC et al. Diagnosing mucopolysaccharidosis IVA. J Inherit Metab Dis. 2013;36(2):293–307. 15. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2013. 16. Harmatz P et al. for MPS VI Phase 3 Study Group. 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. 2006;148(4):533–539. 17. Harmatz P et al. for MPS VI Study Group. 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. 2008;94(4):469–475. 18. Harmatz P et al. 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. 2010;33(1):51–60.
References: 1. Agency for Healthcare Research and Quality. Defining the PCMH. https://pcmh.ahrq.gov/page/defining-pcmh. Accessed December 15, 2015. 2. Hendriksz CJet al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. 3. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144(suppl 5):S27–S34. 4. Muenzer J et al. International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009;123(1):19–29. 5. Neufeld EF et al. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 3. 8th ed. New York: McGraw-Hill; 2002:2465–2494. 6. Scarpa M et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis. 2011;6:72. 7. James A et al. The oral health needs of children, adolescents and young adults affected by a mucopolysaccharide disorder. JIMD Rep. 2012;2:51–58. 8. Coutinho MF et al. Glycosaminoglycan storage disorders: a review. Biochem Res Int. 2012;2012:471325. 9. Kakkis ED et al. The mucopolysaccharidoses. In: Berg BO, ed. Principles of Child Neurology. New York, NY: McGraw-Hill; 1996:1141–1166. 10. Lehman TJA et al. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41–v48.
References: 1. Wold SM et al. Role of the pediatric otolaryngologist in diagnosis and management of children with mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2010;74(1):27–31. 2. Harmatz P et al. The Morquio A clinical assessment program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab. 2013;109(1):54–61. 3. Walker R et al. Anaesthesia and airway management in mucopolysaccharidosis. J Inherit Metab Dis. 2013;36(2):211–219. 4. Hendriksz CJ et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. 5. Lavery C et al. Mortality in patients with Morquio syndrome A. J Inherit Metab Dis Rep. 2015;15:59-66. 6. Theroux MC et al. Anesthetic care and perioperative complications of children with Morquio syndrome. Paediatr Anaesth. 2012;22(9):901–907. 7. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144(suppl 5):S27–S34. 8. Scarpa M et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis. 2011;6:72. 9. Solanki GA et al. Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management. J Inherit Metab Dis. 2013;36(2):339–355. 10. Vitale MG et al. Delphi Consensus Report: Best practices in intraoperative neuromonitoring in spine deformity surgery: development of an intraoperative checklist to optimize response. Spine Deformity. 2014;2(5):333–339. 11. Solanki GAet al. A multinational, multidisciplinary consensus for the diagnosis and management of spinal cord compression among patients with mucopolysaccharidosis VI. Mol Genet Metab. 2012;107:15-24. 12. Spinello CM et al. Anesthetic management in mucopolysaccharidoses. ISRN Anesthesiol. 2013;2013:1–10.