What is the treatment for Hunter syndrome?

Treatment of Hunter Syndrome

Enzyme replacement therapy (ERT) with idursulfase (Elaprase) at 0.5 mg/kg administered intravenously once weekly is the primary treatment for Hunter syndrome. 1

Disease Overview

Hunter syndrome (Mucopolysaccharidosis II or MPS II) is an X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), which results in accumulation of glycosaminoglycans in tissues and organs throughout the body. The condition primarily affects males and presents with a spectrum of severity ranging from attenuated to severe phenotypes.

Treatment Options

First-Line Treatment: Enzyme Replacement Therapy

• FDA-approved indication: Idursulfase (Elaprase) is indicated for patients with Hunter syndrome 1
• Dosing: 0.5 mg/kg administered intravenously once weekly 2, 1
• Demonstrated benefits:
  • Improved walking capacity in patients 5 years and older
  • Reduced spleen and liver volumes (80% of patients with hepatosplenomegaly normalized after 53 weeks of treatment) 1
  • Improved forced vital capacity
  • Increased exercise tolerance as measured by 6-minute walk test
  • Significant improvement in joint mobility
  • Reduction in urinary glycosaminoglycan levels (52% reduction from baseline) 2, 1

Important Considerations with ERT

• Limitations: Idursulfase cannot cross the blood-brain barrier and therefore cannot affect cognitive decline 2

• Age considerations:

  • Approved for patients 5 years and older with demonstrated improvement in walking capacity
  • In patients 16 months to 5 years, treatment reduces spleen volume but lacks data on improvement in disease-related symptoms or long-term clinical outcomes
  • Safety and efficacy not established in children under 16 months 1

• Adverse reactions:

  • Hypersensitivity reactions occur in approximately 69% of patients receiving weekly treatment 1
  • Common reactions include pyrexia, rash, headache, pruritus, urticaria, and musculoskeletal pain
  • Most hypersensitivity reactions can be managed by slowing infusion rate or temporarily stopping the infusion, with or without antihistamines and corticosteroids 1

• Immunogenicity:

  • About 51% of patients develop anti-idursulfase IgG antibodies
  • 41% of antibody-positive patients develop neutralizing antibodies
  • Patients with complete gene deletion, large gene rearrangement, nonsense, frameshift, or splice site mutations are more likely to experience hypersensitivity reactions and serious adverse events compared to those with missense mutations 1

Hematopoietic Stem Cell Transplantation (HSCT)

• Not currently recommended as first-line treatment for Hunter syndrome due to:

  • Inability to preserve neurocognitive outcomes
  • High mortality rate
  • All cases of "severe" MPS II followed by the North American Storage Disease Collaborative Study Group showed declines in IQ to below 50 2

• HSCT has shown some benefits including:

  • Elimination of hepatosplenomegaly
  • Reduction in cardiac valvular thickening
  • Improved joint mobility
  • Normalization of coarse facial features 2

• Some research groups are investigating early HSCT in patients whose older siblings manifested severe disease, but this remains investigational 2

Diagnostic Confirmation

For patients suspected of having Hunter syndrome, the diagnostic algorithm includes:

1. Initial screening with urinary glycosaminoglycan measurement
2. Confirmatory testing with plasma IDS enzyme activity
3. Genetic testing of the IDS gene to identify mutations 2

Multisystem Management

Beyond specific enzyme replacement therapy, management should address the multisystem manifestations:

• Respiratory: Management of sleep apnea, frequent infections
• Cardiovascular: Monitoring and management of cardiac valve disease
• Musculoskeletal: Surgical interventions for carpal tunnel syndrome, joint contractures
• Neurological: Management of hydrocephalus, spinal cord compression
• Gastrointestinal: Repair of hernias (inguinal/abdominal) 3, 4

Monitoring Treatment Response

Regular monitoring should include:

• Urinary glycosaminoglycan levels
• Liver and spleen size assessment
• Pulmonary function tests
• 6-minute walk test
• Evaluation for antibody development 2, 1

Important Knowledge Gaps

Current knowledge gaps that affect treatment decisions include:

• Long-term outcomes data for ERT
• Benefits and harms of initiating ERT soon after birth
• Effectiveness of early HSCT with or without adjunctive ERT 2

Pitfalls to Avoid

• Delayed diagnosis: Early diagnosis is critical before irreversible organ damage occurs 5
• Overlooking attenuated phenotypes: Patients without cognitive impairment may have subtle presentations that are easily missed 5
• Inadequate management of infusion reactions: Proper protocols should be in place to manage hypersensitivity reactions 1
• Unrealistic expectations: ERT improves somatic manifestations but cannot reverse cognitive decline due to inability to cross the blood-brain barrier 2