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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

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 mucopolysaccharidosis (MPS) disorders, hinges on the efficient coordination of each patient’s healthcare team by a medical home.1

Geneticists and/or metabolic specialists are typically at the center of the medical home and help to coordinate multidisciplinary care and an individualized management plan.2,3

Given that ENT manifestations are common in MPS, and often appear early in the disease course, the ENT specialist plays an essential role in the multidisciplinary medical team.4,5

  • Patients with MPS require regular monitoring of oxygen saturation and sleep3
  • Surgeries to correct ENT-related symptoms are common in MPS4, and are often performed earlier in patients with MPS than in the general population
  • Since patients with MPS are at elevated risk of surgical and anesthetic complications, it is essential to be aware of best practices in surgical preparation and perioperative care specific to MPS6
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.3,7
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Many MPS disorders have available management guidelines and specialty-specific consensus recommendations regarding lifelong management of MPS. Guidelines typically recommend the following3,7:

  • 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

Because ENT symptoms often manifest at an early age, the otolaryngologist is in a prime position to initiate diagnosis and refer for confirmation with genetic testing.5 Early and ongoing assessments from a coordinated care team can improve patient outcomes and may help prevent irreversible damage.7

The complexity of MPS disorders often requires early, aggressive intervention for ENT manifestations5

Due to glycosaminoglycan buildup in the ear, patients with MPS have an increased risk of otitis media with effusion and acute otitis media.5,8 Management considerations include the following:

  • Routine otologic and audiologic evaluation3,7
  • Proactive management of otitis media, which is often recurrent9
  • Hearing aids, if appropriate9
  • Ventilation tubes, if appropriate9

Upper airway obstruction results in serious complications for patients with MPS

Upper airway obstruction in patients with MPS can range from varying degrees of sleep apnea to life-threatening airway emergencies. Management strategies for airway obstruction include the following5:

  • Positive airway pressure devices
  • Early adenotonsillectomy
  • Temporary or short-term tracheostomy
Airway obstruction in patients with MPS seriously complicates provision of care and procedural care considerations.

It is important to note that while ENT manifestations and complications are almost universal across MPS types, specific signs and symptoms can differ across and within MPS disorders.5 Individualised management plans should be tailored to specific needs, depending on presenting symptoms and MPS type.

A summary of general and ENT features of MPS syndromes can be found below.

Summary of general and ENT features of MPS syndromes10,11

MPS type
MPS I-H (Hurler)
MPS I-S (Scheie)
MPS I-H/S (Hurler Scheie)
MPS II (Hunter)
MPS IIIA (Sanfilippo, type A)
MPS IIIB (Sanfilippo, type B)
MPS IIIC (Sanfilippo, type C)
MPS IIID (Sanfilippo, type D)
MPS IVA (Morquio A)
MPS IVB (Morquio B)
MPS VI (Maroteaux-Lamy)
MPS VII (Sly)
Main clinical features
Severe Hurler phenotype, mental retardation, corneal clouding, death usually before age 14
Stiff joints, corneal clouding, aortic valve disease, normal intelligence, survival to adulthood
Intermediate phenotype
Severe course, similar to MPS I-H; mild course, milder clinical phenotype, later manifestation, and survival to adulthood with or without mental retardation
Behavioral problems, aggression
Progressive dementia, seizures, survival to second or third decade of life
Considerable interfamilial variability, mild dysmorphism
Coarse hair, clear cornea, usually normal height
Short-trunk type of dwarfism, fine corneal opacities, characteristic skeletal dysplasia and spondyloepiphyseal dysplasia, final height less than 125 cm
Same as Morquio A, but with milder impact on adult height (>120 cm)
Hurler phenotype with marked corneal clouding and normal intelligence; mild, moderate, and severe expression in different families
Highly variable; dense inclusion in granulocytes
Otolaryngologic manifestations
Airway problems, sleep apnoea, upper and lower respiratory tract infections, otitis media, sensorineural hearing loss
Adenotonsillar hypertrophy, airway problems, otitis media, sensorineural hearing loss
Otitis media, adenotonsillar hypertrophy, hearing loss (typically conductive in nature)
Otitis media, adenotonsillar hypertrophy, hearing loss (typically conductive in nature)
Otitis media, adenotonsillar hypertrophy, hearing loss (typically conductive in nature)
Progressive diffuse airway narrowing, adenotonsillar hypertrophy, otitis media, hearing loss (typically conductive in nature)
Otitis media, adenotonsillar hypertrophy, hearing loss (typically conductive in nature)

Adapted from Yueng, Arch Otolaryngol Head Neck Surg, 2009.

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 neurobehavioral and psychiatric evaluations are recommended.7,12,13

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 following:

  • 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 systems7
  • Maintenance and assessment of patients’ ability to perform activities of daily living7
  • 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 paediatrics 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 specialties.3,15 Long-term issues include but are not limited to the following:

  • Best practices in adult-care transition
  • Gynecological 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. ENT manifestations and complications are almost universal across MPS types.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-ophthal

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

  • Specialties represented may include anaesthesiology, pulmonology, neurosurgery, cardiology, ENT, and radiology4,6,7
  • In MPS disorders with neurodegenerative and cognitive implications, additional specialties, 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-ENT

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-ent

Polysomnography is a useful tool for evaluating patients with MPS prior to surgery.1

anesthesia-risk-flowchart-ent
Skeletal and multisystemic complications increase the risk of perioperative morbidity and mortality – guidelines suggest combining surgeries to reduce risk of multiple anesthetic 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 website. http://www.vimizim.com/. Accessed December 21, 2015.  12. BioMarin Pharmaceutical Inc. NAGLAZYME website. 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. Mesolella M, Cimmino M, Cantone E, et al. Management of otolaryngological manifestations in mucopolysaccharidoses: our experience. Acta Otorhinolaryngol Ital. 2013;33(4):267-272.  5. 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.  6. Spinello CM, Novello LM, Pitino S, et al. Anesthetic management in mucopolysaccharidoses. ISRN Anesthesiol. 2013;2013:1-10. doi:10.1155/2013/791983.  7. 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.  8. Simmons MA, Bruce IA, Penney S, Wraith E, Rothera MP. Otorhinolaryngological manifestations of the mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2005;69(5):589-595. doi:10.1016/j.ijporl.2005.01.017.  9. Motamed M, Thorne S, Narula A. Treatment of otitis media with effusion in children with mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2000;53(2):121-124.  10. Yeung AH, Cowan MJ, Horn B, Rosbe KW. Airway management in children with mucopolysaccharidoses. Arch Otolaryngol Head Neck Surg. 2009;135(1):73-79. doi:10.1001/archoto.2008.515.  11. Hendriksz CJ, Harmatz P, Beck M, et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013;110:54-64. doi:10.1016/j.ymgme.2013.04.002.  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. 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.  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.