Hunter syndrome (MPS II) can predispose pediatric patients to repeat respiratory and ear infections, which, often present before Hunter syndrome is diagnosed. 1,2,3 Alongside these recurrent infections, other Hunter syndrome symptoms, including chronic rhinorrhoea, nasal obstruction, noisy breathing, hearing loss and enlarged adenoids and tonsils, in addition to a distended abdomen (hepatosplenomegaly) and chronic diarrhoea, may all contribute to Hunter syndrome, being mistaken to have an infectious/immune-related cause. 4,5,6 Therefore, an undiagnosed Hunter syndrome patient may be referred to an immunologist or allergist to manage the recurrent infections and pulmonary symptoms. 1,2,3 Click here to learn more about the signs and symptoms of Hunter syndrome.

The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) practice parameter for the diagnosis of primary immunodeficiency disorders note the need to exclude the possibility of anatomical or biochemical causes of infection susceptibility, before focusing on investigating immunodeficiency. 7 Click here to download a poster highlighting the key exclusion step in the AAAAI/ACAAI practice parameters.

Biochemical and anatomical changes to airways are an underlying cause of recurrent respiratory infections in Hunter syndrome. 1,8 Hunter syndrome patients may have enlarged tonsils, adenoids, gums and tongue, and tracheomalacia, and thick secretion, including chronic rhinorhoea. 4,8

Click here to read more about the insidious anatomical and biochemical changes that occur in Hunter syndrome, predisposing patients to respiratory infections

Recognising the presence of biochemical and anatomical features of Hunter syndrome that predispose patients to recurrent infections may indicate the need to look for diagnosis outside of immunodeficiency,7 but the key to narrowing in on Hunter syndrome is recognising concurrent multisystemic symptoms, alongside the recurrent infections, such as: 5

  • Hernia – inguinal and umbilical hernias are frequent and often require repair 3,6
  • Organomegaly – enlarged liver and spleen are common 4,6
  • Developmental delays – some patients have a cognitive impairment, first presenting as a delay in development seen by 1.5-2 years of age 9
  • Coarse facial features – dysmorphic facial features are a strong diagnostic feature of Hunter syndrome; however, they may be subtle in some patients 4,5
  • Skeletal dysplasia and joint stiffness – chronic joint stiffness and skeletal dysplasia are among the common early signs of Hunter syndrome, with patients experiencing restricted mobility from a young age 4,6,10
  • Cardiac involvement – some Hunter syndrome patients may have a heart murmur early in the disease course 5. Although heart murmur is often benign, cardiac valve disease is common among patients 11
  • Learn more about how Hunter syndrome is diagnosed

  • Download an informative eBook about Hunter syndrome for Immunologists


  1. Keilmann A et al. Hearing loss in patients with mucopolysaccharidosis II: data from HOS - the Hunter Outcome Survey. J Inherit Metab Dis. 2012; 35(2): 343–353.
  2. Link B et al. Orthopedic manifestations in patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in the Hunter Outcome Survey. Orthop Rev (Pavia). 2010; 2(2): e16.
  3. Mendelsohn NJ et al. Importance of surgical history in diagnosing mucopolysaccharidosis type II (Hunter syndrome): data from the Hunter Outcome Survey. Genet Med. 2010; 12(12): 816–822.
  4. Martin R et al. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. 2008; 121(2): e377–386.
  5. Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr. 2012; 171(4): 631–639.
  6. Wraith JE et al. Initial report from the Hunter Outcome Survey. Genet Med. 2008; 10(7): 508–516.
  7. Bonilla FA et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015; 136(5): 1186–1205.
  8. Bianchi PM et al. ENT and mucopolysaccharidoses. Ital J Pediatr. 2018; 44(Suppl 2): 127.
  9. 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: 267–277.
  10. Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology (Oxford). 2011; 50 Suppl 5: v19–25.
  11. Kampmann C et al. Prevalence and Characterisation of Cardiac Involvement in Hunter Syndrome. J Pediatr. 2011; 159(2): 327–331.