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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

Lifelong management in the new era of MPS

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 and help to coordinate multidisciplinary care and an individualised management plan.2,3

Given the high surgical burden of patients with MPS, which is complicated by the systemic nature of the disease, anaesthesiologists and the operative-care team are essential members of the multidisciplinary medical team.4,5

  • Patients with MPS tend to require frequent surgeries to address the systemic effects of the disease5
  • Successful surgical outcomes require a surgical plan whose key components include presurgical planning and perioperative management consisting of anaesthetic care, continuous monitoring, and postoperative care5
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

Surgical risk assessment and operative planning are critical to sustain and improve long-term clinical outcomes5,7

Skeletal and multisystemic effects of MPS increase the risk of perioperative morbidity and mortality, making ongoing assessment and monitoring essential to decrease the risk of surgical and anaesthetic complications.5,8 Airway obstruction and pulmonary oedema are among the most significant anaesthetic complications, sometimes requiring emergency tracheotomy or reintubation, which can be very challenging.5

Patients with MPS are at elevated risk of complications from anaesthetic and procedural sedation. When possible, general anaesthesia should be avoided and, when necessary, administered only by experienced anaesthesiologists.8,9

Procedural risk associated with necessary sedation and anaesthesia is a critical consideration in imaging modality selection for assessing spinal involvement.8

  • Plain radiography can be a useful initial imaging tool, as it does not require procedural sedation or anaesthesia8
  • After initial imaging evaluation of the spine, subsequent imaging of the spinal cord can be limited to magnetic resonance imaging8
Preparing for surgical and anaesthetic risk with an experienced, multidisciplinary care team can optimise long-term outcomes, as patients with MPS often require multiple surgeries throughout their lifetimes.5

For anaesthesiologists managing anaesthetic care in patients with MPS, consideration should be given to the specific systemic complications presented by the different types of MPS, notably spinal cord compression and airway obstruction.8

  • Anaesthetic treatment plans should include provisions for 3 main contingencies:9
    • Difficult intubation
    • Chronic pulmonary disease
    • Dangerous neck manipulation due to cervical instability
  • The anaesthesiologist should be surrounded by an experienced team and have access to all equipment and support that may be required5

Preparing for surgical and anaesthetic risk in patients with MPS requires an experienced, multidisciplinary care team consisting of anaesthesiology, cardiology, pulmonology, and otolaryngology.5

Anaesthetic risk factors include the following:

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

Operative care considerations across a coordinated team are critical to reducing negative surgical outcomes.5 The table below illustrates these considerations.

Operative-care-considerations-anesth

The anaesthetic risk in patients with MPS is considered high for many reasons, including airway abnormalities, orthopaedic deformities, pulmonary predisposition, and cardiac and neurological involvement.9 Of note, certain MPS disorders may demonstrate greater risk than others, as seen in the table below.

Anesthetic-risk-levels-and-causes

MPS subtype and severity are important indicators of anaesthetic risk and should be taken into consideration prior to surgery. Operative risk is higher in MPS I, II, IV, and VI, with an overall mortality rate of 20%.9

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.6,12,13

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 following3:

  • 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 disease14
    • 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 require careful coordination across specialities.3,15 Long-term issues include but are not limited to the following

  • 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.3,15-17

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. The administration of anaesthesia should be performed only in specialised centres by experienced anaesthesiologists and trained personnel. Indication for surgery should be carried out only after consulting the anaesthesiologist, who has the duty to discuss risks and benefits with patients and their families.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-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

  • 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

Due to the elevated risk of surgical and anaesthetic complications, it is essential to be aware of best practices in surgical preparation and perioperative care specific to MPS. Standard preoperative preparation is insufficient and ineffective for patients with MPS. A complete evaluation of each patient’s specific case must be performed in order to successfully plan for and execute procedures requiring anaesthesia.1

Postoperative monitoring and thorough reassessment is necessary even if patients show sustained improvement following the first year of surgery, as further glycosaminoglycan (GAG) deposition may have altered airway anatomy and cardiac and pulmonary function.1

Accurate preoperative examination requires a variety of analyses1:

  • Laboratory (complete blood count, arterial blood gas analysis, serum electrolyte, and liver enzymes)
  • Pulmonary function (vital capacity, functional residual capacity, and total lung capacity)
  • Cardiac function (electrocardiography, echocardiography, angiography, and cardiac stress test)
  • Airway assessment (tracheobronchoscopy and laryngoscopy)
  • Imaging studies (detailed evaluation of airway morphology by radiograph, computed tomography, magnetic resonance imaging, and/or multidetector computerised tomography)

General anaesthesia is dangerous and should generally be avoided; local anaesthesia with peripheral blocks is preferred whenever possible. Additionally, in order to reduce the risks associated with exposure to multiple anaesthetics, combining two or more diagnostic/surgical interventions during one episode of anaesthesia is advised.1

Postoperative treatment includes steroid prophylaxis to reduce oedema, standard treatment for patients with upper airway obstruction (bilateral positive airway pressure, continuous positive airway pressure), and continuous monitoring of respiratory and cardiac function.1

When emergency surgery is needed, guidelines used for patients with suspected cervical spine injury should be followed.1

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

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.1,9

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. 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.  5. 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.  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. 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.  8. 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.  9. Spinello CM, Novello LM, Pitino S, et al. Anesthetic management in mucopolysaccharidoses. ISRN Anesthesiol. 2013;2013:1–10. doi:10.1155/2013/791983.  10. 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.  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. Neufeld EF, Muenzer J. 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.  13. 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.  14. 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.  15. Coutinho MF, Lacerda L, Alves S. Glycosaminoglycan storage disorders: a review. Biochem Res Int. 2012;2012:471325. doi:10.1155/2012/471325.  16. Kakkis ED, Neufeld EF. The mucopolysaccharidoses. In: Berg BO, ed. Principles of child neurology. New York, NY: McGraw-Hill; 1996:1141–1166.  17. Lehman TJA, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41-v48.

References:  1. Spinello CM, Novello LM, Pitino S, et al. Anesthetic management in mucopolysaccharidoses. ISRN Anesthesiol. 2013;2013:1–10. doi:10.1155/2013/791983.  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.