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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-sulphatase (IDS) gene leading to deficient cleavage of glycosaminoglycans (GAGs), heparan and dermatan sulphate, 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 changes1,2
  • The slowly progressing form of MPS II typically presents between the ages of 4 and 8 years with no cognitive decline and mild somatic changes1,2
Observed presentation
  • Symptoms appear at varying ages2
  • Observed presentation includes the following: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 II3
  • There is a high prevalence of MPS II in the Ashkenazi Jewish population4
  • MPS II is an X-linked recessive disorder, therefore mainly affecting males2
Disease progression
  • Overall disease burden:
    • Patients with the rapidly progressing form of disease experience multiorgan dysfunction, resulting in high disease burden2
    • Patients with the slowly progressing form of disease may present with symptoms and complications that lead to significant morbidity and disability2
    • Both forms of the disease are associated with severe psychological and financial burdens for patients and their families3,5
  • Rapidly progressing MPS II:
    • Symptoms may include: 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:2
      • 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: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 surgery2,3
Genetic information
  • MPS II is caused by mutations in the IDS gene1,2
  • There are over 300 known mutations in the IDS gene6
  • These mutations, and resulting protein dysfunction, lead to accumulation of the GAGs heparan and dermatan sulphate1,2
Key management considerations
  • Enzyme replacement therapy is an important consideration in the management of MPS II2,3
  • Depending on the severity, neurological manifestations are heterogeneous and require their own specific interventions and management2,3
  • Available treatment and management recommendations:
    • Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 2012; 171(4):631–639.
    • Giugliani R 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 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 et al. Clinical practice guideline for the management of Hunter syndrome. Hunter España working group. Med Clin (Barc) 2013;141(10):453.e1–13.
    • Jones SA 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 Dis2009;32(4):534–543.
    • Lampe C 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.
    • Malik V et al. Tracheostomy in mucopolysaccharidosis type II (Hunter’s Syndrome). Int J Pediatr Otorhinolaryngol 2013;77(7):1204-1208.
    • Muenzer J et al. Multidisciplinary management of Hunter syndrome. Pediatrics 2009;124(6):e1228-1239.
    • Muenzer J et al. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr 2012;171(1):181-188.
    • Scarpa 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.
    • Wraith JE 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.
    • Yund B et al. Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. Mol Genet Metab 2015;114(2):170–177.

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References:  1. Hopwood JJ et al. Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate 2-sulphatase gene. Hum Mutat 1993;2(6):435–442.   2. Wraith JE 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.   3. Scarpa 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.  4. Baehner F et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005;28(6):1011–1017.   5. Guffon N et al. 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.  6. Chkioua L et al. Molecular analysis of iduronate -2- sulfatase gene in Tunisian patients with mucopolysaccharidosis type II. Diagn Pathol 2011;6:42.