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MPS Reference
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MPS II: an overview

Patients with mucopolysaccharidosis (MPS) II are at elevated risk for severe morbidity and early mortality1

MPS II, also known as Hunter syndrome, is caused by a genetic mutation in the iduronate 2-sulfatase (IDS) gene leading to deficient cleavage of glycosaminoglycans (GAGs), heparan and dermatan sulfate, which leads to intracellular progressive GAG accumulation with resulting progressive, multisystemic disease.1,2

  • The rapidly progressing form of MPS II typically presents between 18 and 36 months of age with cognitive dysfunction and severe somatic changes.1,2
  • The slowly progressing form of MPS II typically presents between the ages of 4 and 8 years with no cognitive decline and mild somatic changes.1,2

Observed presentation

  • Symptoms appear at varying ages depending on the specific enzyme deficiency and rate of disease progression1:
    • Rapidly progressing, ages 18 to 36 months
    • Slowly progressing, ages 4 to 8 years
  • Observed presentation includes the following 1,3:
    • Change of facial features
    • Enlarged tongue
    • Macrocephaly
    • Hypertrophic tonsils and adenoids
    • Irregularly shaped teeth
    • Recurrent ear infections
    • Hernias
    • Pebbled skin
    • Short stature
    • Joint contractures
    • Changes to musculoskeletal system, eyes, gastrointestinal tract, airways and cardiovascular system
  • Combinations of the above clinical manifestations should prompt testing for MPS II.3
  • There is a high prevalence of MPS II in the Ashkenazi Jewish population.4
  • MPS II is an X-linked recessive disorder, therefore mainly affecting males.2

Disease progression

  • Overall disease burden:
    • Patients with the rapidly progressing form of disease experience multiorgan dysfunction, resulting in high disease burden.2
    • Patients with the slowly progressing form of disease may present with symptoms and complications that lead to significant morbidity and disability.2
    • Both forms of the disease are associated with severe psychological and financial burdens for patients and their families.3,5
  • Rapidly progressing MPS II:
    • Symptoms may include the following 1,2:
      • Cognitive decline with hyperactive and aggressive behaviour
      • Hernia
      • Significant multisystemic complications, including skeletal deformities that can restrict pulmonary function 2,5
    • Left untreated, patients typically die before 15 years of age; mortality is often associated with cardiorespiratory failure and neurological deterioration. 1,2
  • Slowly progressing MPS II:
    • Symptoms appear between 4 and 8 years of age with variable progression and typically include the following2:
      • Short stature
      • Coarse facial features
      • Joint contractures
      • Hernia due to hepatosplenomegaly
    • Left untreated, patients typically die between the ages of 20 and 60 years of age; mortality is often associated with cardiorespiratory failure. 1,2
  • Patients with MPS II typically have a high surgical burden that may include the following 2,3:
    • Myringotomies
    • Hernia surgery, often with repeat procedures
    • Adenoidectomy
    • Tonsillectomy
    • Cervical decompression
    • Carpal tunnel surgery
    • Cardiac valve replacement therapy
    • Hip and knee replacement and correction of lower limb axis
  • Patients with MPS II often experience anaesthetic complications due to obstructed airways; therefore, care must be taken for patients undergoing surgery.2,3

Genetic information

  • MPS II is caused by mutations in the IDS gene.1,2
  • There are over 300 known mutations in the IDS gene.6
  • These mutations, and resulting protein dysfunction, lead to accumulation of the GAGs heparan and dermatan sulfate.1,2

Key management considerations

  • Enzyme replacement therapy is an important consideration in the management of MPS II.2,3
  • Depending on the severity, neurological manifestations are heterogeneous and require their own specific interventions and management.2,3
  • Available treatment and management recommendations:
    • Burton BK, Giugliani R. Diagnosing Hunter syndrome in paediatric practice: practical considerations and common pitfalls. Eur J Paediatr. 2012;171(4):631-639. doi: 10.1007/s00431-012-1703-y.
    • Giugliani R, Federhen A, Muñoz Rojas MV, et al. Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts. Rev Assoc Med Bras. 2010;56(3):271-277.
    • Giugliani R, Federhen A, Rojas MV, et al. Mucopolysaccharidosis I, II and VI: Brief review and guidelines for treatment. Genet Mol Biol. 2010;33(4):589-604. doi:10.1590/S1415-47572010005000093.
    • Giugliani R, Villarreal ML, Valdez CA, et al. Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America. Genet Mol Biol. 2014;37(2):315-329.
    • Guillén-Navarro E, Blasco AJ, Gutierrez-Solana LG, et al. Clinical practice guideline for the management of Hunter syndrome. Hunter España working group. Med Clin (Barc). 2013;141(10):453.e1-13. doi:10.1016/j.medcli.2013.07.010.
    • Jones SA, Almássy Z, Beck M, et al. HOS Investigators. Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS). J Inherit Metab Dis.2009;32(4):534-543. doi:10.1007/s10545-009-1119-7.
    • Lampe C, Bosserhoff AK, Burton BK, et al. Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: an international case series. J Inherit Metab Dis. 2014;37(5):823-829. doi:10.1007/s10545-014-9686-7.
    • Malik V, Nichani J, Rothera MP, et al. Tracheostomy in mucopolysaccharidosis type II (Hunter’s Syndrome). Int J Pediatr Otorhinolaryngol. 2013;77(7):1204-1208. doi:10.1016/j.ijporl.2013.05.002.
    • Muenzer J, Beck M, Eng CM, et al. Multidisciplinary management of Hunter syndrome. Paediatrics. 2009;124(6):e1228-1239. doi:10.1542/peds.2008-0999.
    • Muenzer J, Bodamer O, Burton B, et al. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Paediatr. 2012;171(1):181-188. doi:10.1007/s00431-011-1606-3.
    • Scarpa M, Almássy Z, Beck M, et al. Hunter Syndrome Europena Expert Council. 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.
    • Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Paediatr. 2008;167(3):267-277.
    • Yund B, Rudser K, Ahmed A, et al. Cognitive, medical and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. Mol Genet Metab. 2015;114(2):170-177. doi:10.1016/j.ymgme.2014.12.299.
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References:  1. Hopwood JJ, Bunge S, Morris CP, et al. Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate 2-sulphatase gene. Hum Mutat. 1993;2(6):435-442. doi:10.1002/humu.1380020603.  2. Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008;167(3):267-277. doi:10.1007/s00431-007-0635-4.  3. 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.  4. Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis. 2005;28(6):1011-1017. doi:10.1007/s10545-005-0112-z.  5. Guffon N, Heron B, Chabrol B, Feillet F, Montauban V, Valayannopoulos V. Diagnosis, quality of life, and treatment of patients with Hunter syndrome in the French healthcare system: a retrospective observational study. Orphanet J Rare Dis. 2015; 10:43.doi:10.1186/s13023-015-0259-0.  6. Chkioua L, Khedhiri S, Ferchichi S, et al. Molecular analysis of iduronate -2- sulfatase gene in Tunisian patients with mucopolysaccharidosis type II. Diagn Pathol. 2011;6:42. doi:10.1186/1746-1596-6-42.