Clinical Impact of the Diseases

The enzyme deficiencies that define MPS I and MPS II each produce a continuum of clinical phenotypes ranging from severe to attenuated.1

The biochemically distinct disorders share many signs and symptoms, and although there are some distinguishing features (see Identifying MPS I & II), MPS I and MPS II can be difficult to differentiate clinically.2 Some signs and symptoms are believed to be directly caused by the accumulation of dermatan sulphate and heparan sulphate, whereas others are the result of secondary pathological processes.3

Somatic manifestations occur across the entire clinical spectrums of MPS I and MPS II. Characteristic features include recurrent respiratory infections and airway obstruction, cardiac disease, skeletal deformities and restricted joint movement, disproportionate short stature and characteristic coarse facial features.4,5 Many early signs and symptoms overlap with common childhood complaints and it is usually recognition of a cluster of characteristic signs and symptoms that raises clinical suspicion of an MPS disorder.2

Severe MPS I & II phenotypes

Many individuals with MPS I or MPS II are affected by cognitive involvement in addition to somatic manifestations. The presence of cognitive involvement and profound mental deterioration defines a severe phenotype.6,7 The onset of disease occurs in infancy (MPS I) or early childhood (MPS II) in severely affected patients.4,5,8 Disease progression is rapid and patients are severely mentally handicapped by the time of their death.4,5,9 Children with severe MPS I rarely survive beyond 10 years, whereas children with severe MPS II may reach the age of 20 years. A combination of cardiorespiratory failure and progressive neurologic disease is a common cause of death in each disorder.4,5

Attenuated MPS I & II phenotypes

Individuals with attenuated phenotypes have no or mild cognitive impairment but may experience other neurologic manifestations including carpal tunnel syndrome (CTS) and myelopathy.2,6 Age at disease onset is variable but is generally later than in individuals with severe phenotypes.6,10,11 Patients experience the same somatic manifestations that occur in severe disease, but the rate of progression and combination of organ involvement is more variable.8,11 Symptoms may be subtle and therefore easily missed.1 Cardiac disease and airway obstruction typically shorten survival to early to mid-adulthood, although patients with the most attenuated MPS I phenotypes may reach a normal or near normal lifespan.8,9

You can learn more about the clinical impacts specific to MPS I and MPS II in Signs and symptoms.

References

  1. 1.Muenzer J. (2011) Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 50 Suppl 5: v4-12.
  2. 2.Burton BK, Giugliani R. (2012) Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 171(4): 631-639.
  3. 3.Campos D, Monaga M. (2012) Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms. Metab Brain Dis 27(2): 121-129.
  4. 4.Wraith JE, Scarpa M, Beck M, et al. (2008) Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr 167(3): 267-277.
  5. 5.Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on M, Treatment of Mucopolysaccharidosis I. (2009) Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 123(1): 19-29.
  6. 6.Beck M, Arn P, Giugliani R, et al. (2014) The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med 16(10): 759-765.
  1. 7.Wraith JE, Beck M, Giugliani R, et al. (2008) Initial report from the Hunter Outcome Survey. Genet Med 10(7): 508-516.
  2. 8.Neufeld EF, Muenzer J. The Mucopolysaccharidoses In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2014.
  3. 9.Young ID, Harper PS, Newcombe RG, Archer IM. (1982) A clinical and genetic study of Hunter's syndrome. 2. Differences between the mild and severe forms. J Med Genet 19(6): 408-411.
  4. 10.Young ID, Harper PS. (1982) Mild form of Hunter's syndrome: clinical delineation based on 31 cases. Arch Dis Child 57(11): 828-836.
  5. 11.Thomas JA, Beck M, Clarke JT, Cox GF. (2010) Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. J Inherit Metab Dis 33(4): 421-427.