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When available, enzyme replacement therapy (ERT) is the first step to optimal outcomes

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 mucopolysaccharidosis (MPS) I, II, IVA, and VI8,9
  • Clinical trials investigating the feasibility and potential benefits of ERT in other MPS disorders are ongoing
  • When available, home-based infusion of ERT is an important clinical consideration10-12
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Management guidelines and expert reviews on MPS disorders call for initiation of ERT, when available, as soon as diagnosis is confirmed.6,8,13

Lifelong management in the new era of MPS

The new era of management for progressive, complex, genetic conditions, such as MPS disorders, hinges on the efficient coordination of each patient’s healthcare team.1

Geneticists and/or metabolic specialists are typically at the centre and help to coordinate multidisciplinary care and an individualised management plan.2,3

Respiratory disorders occur in all MPS types; pulmonologists have a crucial role in the multidisciplinary management team.3,4

  • Anticipation and early management of respiratory dysfunction is a key component to optimising overall clinical outcomes4,5
  • Baseline assessments of respiratory function are critical at diagnosis and prior to initiation of ERT4,5
In patients with MPS disorders, the benefits of coordinated care may improve many aspects of a patient’s — and a family’s — outlook over the long term.3,6
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Many MPS disorders have available management guidelines and speciality-specific consensus recommendations regarding lifelong management of MPS. Guidelines typically recommend:3,6

  • Comprehensive baseline assessments (e.g. speciality-specific evaluations, functional performance, and disease burden) by appropriate specialists
  • Regular, defined monitoring intervals to assess multisystemic disease progression

Early and ongoing assessments from a coordinated-care team can improve patient outcomes and may help prevent irreversible damage.6

Respiratory dysfunction occurs in all MPS types and should be continually monitored5

Many respiratory manifestations in MPS are related to glycosaminoglycan (GAG) deposits, which can cause airway obstruction.4 Upper airway obstruction in patients with MPS can range from varying degrees of sleep apnoea to life-threatening airway emergencies. Management strategies for airway obstruction include:7

  • Continuous or bilevel positive airway pressure devices (CPAP/BiPAP)
  • Early adenotonsillectomy
  • Temporary or long-term tracheostomy
Airway obstruction seriously complicates procedural care considerations such as anaesthesia and surgical interventions in patients with MPS.7
Generally, obstructive symptoms are initially more prominent in the upper airway. For pulmonologists managing patients with MPS, an understanding of the complex clinical picture of respiratory manifestation in this population, combined with frequent assessment, is essential to positive clinical outcomes.4,5

Overview of MPS types and key respiratory manifestations

Overview-of-MPS-types-and-key-respiratory-manifestations

The ENT and respiratory disorders of MPS can be divided into airway abnormalities, alterations in respiratory mechanics, and effects of sleep, as demonstrated in a study including 21 patients with MPS I, II, IV, VI, and VII.

Manifestations-of-MPS-that-may-affect-respiratory-function

Respiratory involvement is heterogeneous across patients and MPS subtypes4

A number of interventions and considerations exist for patients with MPS who have ongoing respiratory complications:

  • Inhaled steroids may decrease airway inflammation in patients with lower airway obstruction5
  • Patients are more likely to benefit from early and aggressive treatment of respiratory tract infection5
  • Regular vaccinations for pneumococcus and influenza are an important part of supportive therapies for optimal respiratory health5
  • Corticosteroids and anticholinergic bronchodilators may be useful; patients with tracheal and bronchial wall instability may not respond well to
    beta-agonists5
  • Decompression surgery may improve restrictive pulmonary disease by alleviating spinal cord compression5
  • Sleep apnoea may be treated by surgery (e.g. adenotonsillectomy), by CPAP or BiPAP, or by tracheotomy in extreme cases4

Routine evaluations by a pulmonologist are an important part of disease management4

The timing of initial consultation and frequency of visits should be tailored to disease type and severity of symptoms. Most patients should be seen following diagnosis and then every 6 to 12 months.4

Routine lung function evaluation should include:4

  • Assessment of obstructive symptoms during sleep and wakefulness
  • Assessment of restrictive lung disease and exercise limitations
  • Spirometry and lung volume measurements (e.g. vital capacity [VC], forced vital capacity in 1 second [FEV1], maximum voluntary ventilation [MVV])
  • Assessment for symptoms of sleep apnoea or disturbances
  • Inquiry regarding upcoming surgery to ensure that the respiratory specialist is involved in preoperative planning
Because lung function testing has been used to measure the impact of ERT on select MPS disorders, it is critical to attain baseline values as soon as a diagnosis is made.6,8

Respiratory specialists should be involved in any surgeries or sedations planned in patients with MPS4

Because patients with MPS are at elevated risk of complications from anaesthetic and procedural sedation, it is important that an anaesthesiologist who has experience with patients with MPS patients be a part of the surgical team.4 A respiratory specialist should be involved both before and after surgery.4,9

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:

  • Discussing the risks and benefits of intervention and necessary precautions with treatments and evaluations3
  • Dental considerations
    • The wide range of craniofacial and dental abnormalities, which varies by MPS subtype may or may not predispose patients to an increased risk of dental disease10
    • Close monitoring of dental development (at least annually) and regular dental care to prevent caries and attrition of the teeth3
  • Overall health interventions, which may include supportive therapies such as regular influenza and pneumococcus vaccinations, bronchodilators and aggressive and prompt treatment of upper respiratory infections3

Speciality-specific assessments, as well as regular physical examinations and overall health interventions, should follow recommended guidelines, which may vary among MPS subtypes.3

Continuity of care into adulthood optimises long-term outcomes

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.3 Physicians should ensure the following:

  • Early and ongoing assessments from a coordinated-care team to evaluate disease progression across organ systems6
  • Maintenance and assessment of patient’s ability to perform activities of daily living6
  • Formal, site-specific transition strategies, including identification of adult specialists with long-term MPS management experience3
  • That patients are not lost to follow-up3
Encourage patients and their families to be involved in site-specific transition strategies, which can be tailored to optimise each individual’s long-term care plan.3

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.3 Long-term care considerations are ideally best addressed in a centre with significant MPS experience, and they require careful coordination across specialities.3,11 Long-term issues include but are not limited to:

  • Best practices in adult-care transition
  • Gynaecological considerations
    • Pregnancy and maternity-related issues
    • ERT use during pregnancy and lactation
  • Long-term port management
  • Long-term pain management

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.3,11-13

Procedural care requires coordinated surgical planning across specialities

Because clinical manifestations of mucopolysaccharidosis (MPS) disorders are multisystemic, a patient-specific, multidisciplinary approach is required to proactively recognise and manage complications. Pulmonologists play an important role in pre- and post-surgical planning.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

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Surgical-burden-in-patients-with-Morquio-A-default

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

  • Specialities represented may include anaesthesiology, pulmonology, neurosurgery, cardiology, ENT, and radiology4,6,7
  • In MPS disorders with neurodegenerative and cognitive implications, additional specialities, such as psychiatry and neurology, may be involved8
  • In addition to the management guidelines, specialists should consult orthopaedic and surgical guidelines

Preparing for surgical and anaesthetic risk in patients with MPS requires an experienced, multidisciplinary care team consisting of anaesthesiology, cardiology, pulmonology, and otolaryngology.3

Anaesthetic risk factors include the following, outlined in the figure below.

Overview-of-anesthetic-risk-factors-in-patients-with-MPS-anesth

Surgical risk assessment and operative planning are critical

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

Operative-care-considerations-pulm

Additional pre- and post-surgical considerations specific to pulmonology should be taken into account:1

Pre-surgical

  • Counselling to patients and caregivers on the risk of emergency tracheotomy
  • Pre-surgical assessment, including the following:
    • History of prior anaesthesia
    • Symptoms of airway obstruction
    • Further tests, if necessary:
      • Spirometry
      • X-rays
      • Neck soft-tissue radiography to evaluate pharyngeal narrowing in wakefulness
      • Evaluation for obstructive sleep apnoea using polysomnography
      • Radiography to investigate cervical spine instability
    • A plan for airway management during surgery

Post-surgical

  • Monitoring for postoperative complications:
    • Laryngeal or subglottic oedema, particularly in the case of multiple intubations
    • Swelling and respiratory compromise, even as late as 24 hours postoperatively
    • Pulmonary oedema
Prior to any sedation or anaesthesia, pulmonologists should provide counseling to patients and families, including discussion of the risk of emergency tracheotomy.1
anesthesia-risk-flowchart-anesth
Skeletal and multisystemic complications increase the risk of perioperative morbidity and mortality. Guidelines suggest combining surgeries to reduce risk of multiple anaesthetic episodes. Identify risks to lower the likelihood of surgical complications in MPS disorders.9,12

Optimise patient outcomes through coordinated management.

It's a new era in management. Stay informed about the latest updates and information about MPS.

References:  1. McGill JJ, Inwood AC, Coman DJ, et al. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age – a sibling control study. Clin Genet. 2010;77(5):492–498. doi:10.1111/j.1399-0004.2009.01324.x.  2. Furujo M, Kubo T, Kosuga M, Okuyama T. Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI. Mol Genet Metab. 2011;104(4):597–602. doi:10.1016/j.ymgme.2011.08.029.  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, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41–v48.  5. Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v19–v25. doi:10.1093/rheumatology/ker397.  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. doi:10.1016/j.ymgme.2013.11.015.  9. Hendriksz CJ, Berger KI, Giugliani R, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. doi:10.1002/ajmg.a.36833.  10. Bagewadi S, Roberts J, Mercer J, Jones S, Stephenson J, Wraith JE. 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. doi:10.1007/s10545-008-0980-0.  11. BioMarin Pharmaceutical Inc. VIMIZIM Web site. http://www.vimizim.com/. Accessed December 21, 2015.  12. BioMarin Pharmaceutical Inc. Naglazyme Web site. http://www.naglazyme.com/. Accessed December 21, 2015.  13. Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009;123(1):19–29. doi:10.1542/peds.2008-0416.

References:  1. Agency for Healthcare Research and Quality. Defining the PCMH. https://pcmh.ahrq.gov/page/defining-pcmh. Accessed December 15, 2015.  2. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144(suppl 5):S27-S34.  3. Hendriksz CJ, Berger KI, Giugliani R, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. doi:10.1002/ajmg.a.36833.  4. Muhlebach MS, Wooten W, Muenzer J. Respiratory manifestations in mucopolysaccharidoses. Paediatr Respir Rev. 2011;12(2):133–138. doi:10.1016/j.prrv.2010.10.005.  5. Berger KI, Fagondes SC, Giugliani R, et al. Respiratory and sleep disorders in mucopolysaccharidosis. J Inherit Metab Dis. 2013;36(2):201–210. doi:10.1007/s10545-012-9555-1.  6. Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009;123(1):19–29. doi:10.1542/peds.2008-0416.  7. Wold SM, Derkay CS, Darrow DH, Proud V. Role of the pediatric otolaryngologist in diagnosis and management of children with mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2010;74(1):27–31. doi:10.1016/j.ijporl.2009.09.042.  8. Hendriksz C. Improved diagnostic procedures in attenuated mucopolysaccharidosis. Br J Hosp Med. 2011;72(2):91–95.  9. Solanki GA, Martin KW, Theroux MC, 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. doi:10.1007/s10545-013-9586-2.  10. James A, Hendriksz CJ, Addison O. The oral health needs of children, adolescents and young adults affected by a mucopolysaccharide disorder. JIMD Rep. 2012;2:51–58. doi:10.1007/8904_2011_46.  11. Coutinho MF, Lacerda L, Alves S. Glycosaminoglycan storage disorders: a review. Biochem Res Int. 2012;2012:471325. doi:10.1155/2012/471325.  12. Kakkis ED, Neufeld EF. The mucopolysaccharidoses. In: Berg BO, ed. Principles of child neurology. New York, NY: McGraw-Hill; 1996:1141–1166.  13. Lehman TJA, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41-v48.

References:  1. Muhlebach MS, Wooten W, Muenzer J. Respiratory manifestations in mucopolysaccharidoses. Paediatr Respir Rev. 2011;12(2):133–138. doi:10.1016/j.prrv.2010.10.005.  2. Harmatz P, Mengel KE, Giugliani R, 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. doi:10.1016/j.ymgme.2013.01.021.  3. Walker R, Belani KG, Braunlin EA, et al. Anaesthesia and airway management in mucopolysaccharidosis. J Inherit Metab Dis. 2013;36(2):211–219. doi:10.1007/s10545-012-9563-1.  4. Hendriksz CJ, Berger KI, Giugliani R, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet Part A. 2014;9999A:1–15. doi:10.1002/ajmg.a.36833.  5. Lavery C, Hendriksz C. Mortality in patients with Morquio syndrome A. J Inherit Metab Dis Rep. 2015;15:59–66. doi:10.1007/8904_2014_298.  6. Theroux MC, Nerker T, Ditro C, Mackenzie WG. Anesthetic care and perioperative complications of children with Morquio syndrome. Paediatr Anaesth. 2012;22(9):901–907. doi:10.1111/j.1460-9592.2012.03904.x.  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, Almassy Z, Beck 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. doi:10.1186/1750-1172-6-72.  9. Solanki GA, Martin KW, Theroux MC, 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. doi:10.1007/s10545-013-9586-2.  10. Vitale MG, Skaggs DL, Pace GI, 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. doi:10.1016/j.jspd.2014.05.003.  11. Solanki GA, Alden TD, Burton BK, et 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. doi:10.1016/j.ymgme.2012.07.018.  12. Spinello CM, Novello LM, Pitino S, et al. Anesthetic management in mucopolysaccharidoses. ISRN Anesthesiol. 2013;2013:1–10. doi:10.1155/2013/791983.