Back to Top

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
GMS-inner1
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.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 prevalence of ocular manifestations and the potential for surgical intervention related to corneal transplant, ophthalmologists should play a role in the multidisciplinary medical team.4

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.3,5

Many MPS disorders have available management guidelines and
speciality-specific consensus recommendations regarding lifelong management of MPS. Guidelines typically recommend the following:3,5

  • 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.5

GMS-inner1

Guidelines for the general MPS population recommend assessing ophthalmological function upon diagnosis and when triggered by clinical abnormalities.3,6

Given the progressive nature of MPS and the high risk of ocular manifestations in patients with the disease, it is recommended that paediatricians refer children with MPS for ocular assessment at the time of diagnosis, then every 6 to 12 months during preschool age and then annually until 18 years of age.4 In addition to annual eye examinations, ophthalmologists should perform regular assessments of the following:6

  • Fundi, with photographs if possible
  • Strabismus
  • Visual acuity
  • Refraction and intraocular pressure (IOP) (recommended for patients with MPS VI)
  • Visual field changes in case of changes in optic nerve appearance or increased IOP
Symptoms such as headache, sudden visual loss, strabismus, diplopia, increasing photosensitivity and/or nyctalopia can be indications of the need for urgent and more frequent examinations.4

The table below details the basic and optional tests for ocular assessment of children with MPS.

Recommended-ocular-assessments-for-children-with-MPS
Ophthalmologists should be aware of potential difficulties with certain ongoing assessments:4
  • Visual field can be difficult to assess because of poor cooperation
  • IOP may also be falsely high because of corneal rigidity
  • Glaucoma is often difficult to diagnose because of corneal opacities

These diagnostic problems may help to explain why there is limited knowledge of the benefits and risks associated with antiglaucoma therapy in children with MPS. Some reports showed improvements in IOP or vision after medical or surgical treatment of glaucoma, while others had less successful outcomes.4

For further detail regarding these basic and optional ocular assessments in children with MPS, consult the management guidelines.

Ongoing monitoring can help to optimise patient outcomes through long-term management of ocular symptoms, which may include:4

  • High hyperopia
  • Corneal clouding
  • Peripheral vascularisation of the cornea
  • Retinopathy
  • Glaucoma
  • Optic nerve swelling and atrophy
  • Progressive pseudo-exophthalmos
  • Hypertelorism
  • Amblyopia
  • Strabismus

Nonocular causes of visual impairment, such as cerebral visual impairment, may also occur in patients with MPS.4

Simple interventions such as the use of prescription glasses or photochromatic glasses can considerably improve quality of life in children with MPS.4

Of note, ocular manifestations have been described in all subtypes of MPS, but are particularly common in patients with MPS I, VI, and VII.4

  • Over 90% of patients with MPS I and MPS VI have hyperopia4
  • Ocular motility problems are relatively common among MPS subtypes and could be secondary to reduced vision from multiple causes, including optic pathway damage attributed to increased intracranial pressure or to abnormal orbits4

Given the phenotypic differences across and within MPS subtypes, ocular assessments should be tailored to the patient’s individual situation, taking into account his or her age and the presence of influencing factors such as:4

  • Severe photophobia
  • Corneal clouding
  • Poor cooperation due to intellectual disability or behavioural disorders

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.5,7,8

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 disease9
    • 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 systems5
  • Maintenance and assessment of patient’s ability to perform activities of daily living5
  • 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.3,10 Long-term issues include but are not limited to:

  • Best practices in adult-care transition
  • Gynaecological considerations
    • Pregnancy- and maternity-related issues
    • Enzyme replacement therapy (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.3,10-12

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 such as corneal transplant, which may be necessary in patients with MPS.1,2

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.3

GMS-inner1
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.3-5 For example, surgical complications resulted in an 11% mortality rate in patients with Morquio A (n=27).6

Creating a surgical plan is crucial and involves a multidisciplinary team of specialists who are, ideally, also experienced in treating patients with MPS.4

  • Specialities represented may include anaesthesiology, pulmonology, neurosurgery, cardiology, ENT, and radiology1,5,7
  • 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.

In patients with MPS who may consider corneal transplant and treatment of glaucoma, the benefits should be carefully balanced against the risks2

The expected benefits of corneal transplant in patients with corneal clouding should be weighed against the risks of this procedure, which include:2

  • The presence of concomitant retinopathy, glaucoma, or optic nerve disease, which may limit restoration of vision
  • The risks of general anaesthesia (due to concomitant cardiopulmonary problems, cervical spine instability and intubation difficulty) and the patient’s ability to cope with the postoperative management

Overall, the benefits and risks of ocular procedures in patients with MPS are less well understood.2

  • Most often, penetrating keratoplasty is successful, but isolated reports suggest that recurrent opacification may occur2
  • Recent reports have also shown successful outcomes with deep anterior lamellar keratoplasty in children with MPS2

As is the case with corneal clouding, ophthalmologists should weigh the chance of successful outcome of treatment against the potential risks when deciding on management of glaucoma in children with MPS.2

The progressive nature of MPS and the multiple complications that may arise when treating ocular problems in children with MPS necessitate careful coordination and continual monitoring of the impact of any treatment.2

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.4,9,10

Operative-care-considerations-ophthal
anesthesia-risk-flowchart-ophthal
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. Fahnehjelm KT, Ashworth JL, Pitz S, et al. Clinical guidelines for diagnosing and managing ocular manifestations in children with mucopolysaccharidosis. Acta Ophthalmol. 2012;90(7):595–602. doi:10.1111/j.1755-3768.2011.02280.x.  5. 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.  6. Ashworth JL, Kruse FE, Bachmann B, et al. Ocular manifestations in the mucopolysaccharidoses – a review. Clin Experiment Ophthalmol. 2010;38(suppl 1):12–22. doi:10.1111/j.1442-9071.2010.02364.x.  7. Neufeld EF, Muenzer J. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:3421-3452.  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. 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.  10. Coutinho MF, Lacerda L, Alves S. Glycosaminoglycan storage disorders: a review. Biochem Res Int. 2012;2012:471325. doi:10.1155/2012/471325.  11. Kakkis ED, Neufeld EF. The mucopolysaccharidoses. In: Berg BO, ed. Principles of child neurology. New York, NY: McGraw-Hill; 1996:1141–1166.  12. Lehman TJA, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v41–v48.

References:  1. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144(suppl 5):S27-S34.  2. Fahnehjelm KT, Ashworth JL, Pitz S, et al. Clinical guidelines for diagnosing and managing ocular manifestations in children with mucopolysaccharidosis. Acta Ophthalmol. 2012;90(7):595–602. doi:10.1111/j.1755-3768.2011.02280.x.  3. 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.  4. 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.  5. 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.  6. 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.  7. 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.  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.