Hunter's syndrome (MPS-2)

❗ Hunter’s Syndrome (MPS II) is a lysosomal storage disorder due to iduronate-2-sulfatase deficiency. 📌 Dysostosis multiplex = constellation of skeletal abnormalities (short stature, thick ribs, spine deformity, hepatosplenomegaly). 🔎 Remember: Unlike other MPS, Hunter’s has no corneal clouding.

📖 About

• Hunter's syndrome (MPS II) is a rare lysosomal storage disorder within the Mucopolysaccharidoses (MPS) group.
• Inheritance: X-linked recessive → almost exclusively affects males (contrast with most other MPS, which are autosomal recessive).
• Incidence: ~1 in 100,000–170,000 live male births.
• Pathology: Progressive accumulation of dermatan sulfate & heparan sulfate in multiple organs → multisystem disease.

🧬 Aetiology

• Deficiency of iduronate-2-sulfatase (I2S) due to mutations in the IDS gene.
• Results in impaired breakdown of glycosaminoglycans (GAGs).
• Progressive accumulation → skeletal, cardiac, respiratory, and CNS complications.

🩺 Clinical Features

• Coarse facies: Large head, broad nose, thick lips, macroglossia, thick skin.
• Dysostosis multiplex: Short stature, joint stiffness, thoracic cage deformity, gibbus deformity of spine.
• CNS: Intellectual disability (severe form), hyperactivity, behavioral problems. ⚡ But mild subtype may have near-normal intellect.
• Ocular: ❌ No corneal clouding (contrast with Hurler’s, MPS I).
• Cardio-respiratory: Valvular heart disease, obstructive airway disease, sleep apnoea, recurrent chest infections.
• Other: Hepatosplenomegaly, progressive hearing loss.
• ⚠️ Severe form → death in adolescence from cardiorespiratory failure. Milder form → survival into adulthood but with major morbidity.

🧪 Investigations

• Urinary GAGs: ↑ Dermatan sulfate & heparan sulfate.
• Enzyme assay: Low/absent iduronate-2-sulfatase activity in leukocytes or fibroblasts.
• Genetic testing: IDS gene mutation analysis (definitive).
• Imaging: X-rays show dysostosis multiplex; MRI for spinal cord compression & brain involvement.
• Cardiac echo & sleep studies: For cardiopulmonary assessment.

💊 Management

• Supportive: Physiotherapy, shunts for hydrocephalus, orthopaedic surgery, hearing aids, cardiac monitoring.
• Enzyme Replacement Therapy (ERT): Idursulfase (Elaprase) → slows progression, improves hepatosplenomegaly & mobility but does not cross the BBB (so limited effect on CNS decline).
• Haematopoietic stem cell transplantation (HSCT): Trialled but less successful than in Hurler’s syndrome.
• Gene therapy: Currently under research; promising but not standard of care.
• 💡 Lifelong multidisciplinary care required (metabolic team, cardiology, respiratory, orthopaedics, ENT, physiotherapy).

📊 Exam Comparison: Hurler vs Hunter

🧠 Memory Aid

• “Hunter’s has no cloudy corneas, but patients may be aggressive hunters.” → mnemonic for absence of corneal clouding & behavioral issues.

🧾 Clinical Case Example – Hunter’s Syndrome (MPS II)

A 6-year-old boy is referred with developmental delay and behavioural problems. Parents report noisy breathing, recurrent ear infections, and coarse facial features that have become more obvious with age. Exam shows a broad nose, thick lips, enlarged tongue, short stature, and joint stiffness. Hepatosplenomegaly is present. Unlike Hurler’s syndrome, there is no corneal clouding. Family history: maternal uncle with similar features. 🧪 Urine glycosaminoglycans: dermatan and heparan sulphate elevated. Enzyme assay: iduronate-2-sulfatase deficiency. Genetic testing confirms X-linked inheritance. 👉 Diagnosis: Hunter’s syndrome (Mucopolysaccharidosis type II). 👉 Management: Enzyme replacement therapy (idursulfase), supportive care (ENT, cardiology, physiotherapy), genetic counselling for family.