Information for Neurologists

MPS I can affect many different organ systems and patients generally see several specialists before getting a diagnosis. Because neurological involvement is typical in severe MPS I patients, referral to a neurologist is likely. Below are presenting symptoms observed by neurologists that may lead to clinical suspicion of MPS I and warrant more definitive testing.

Bilateral dyestesia

People with both severe and attenuated forms of MPS I sometimes experience pain and loss of feeling in their fingertips as a result of carpal tunnel syndrome (median nerve entrapment).[1]  This syndrome is due to pressure on the median nerve as a result of thickened ligaments within the wrist; it may cause pain, and loss of feeling in the fingertips, but most patients lack these typical symptoms (pain, tingling, or numbness).[3],[4],[5] Because of the high incidence of the syndrome, routine electromyographic/nerve conduction velocity testing is typically recommended by the treating physician, even in the absence of patient complaints.[5]

Bilateral DyestesiaCredit: Illustration courtesy of the National MPS Society

Developmental delay

Patients with MPS I manifest a wide range of intellectual involvement. MPS I patients will suffer progressive and profound mental retardation, while patients on the attenuated end of the disease spectrum will exhibit little or no intellectual dysfunction.[6]  In severe patients historically known as Hurler patients, early development may be normal but developmental delay is usually suspected by 12 months.[6]  Thereafter, there is usually progressive deterioration, and by 18 months, developmental delay is usually apparent. From this point on, patients generally do not progress in development but plateau for a number of years followed by a slow decline in intellectual capabilities.

Hydrocephalus

In addition to the direct CNS effects of MPS I, communicating hydrocephalus is common. Decreased resorption of cerebrospinal fluid by arachnoid villi causes an associated increase in intracranial pressure, leading to brain compression. Rapidly increasing pressure may be the cause of acute developmental decline in some patients. Symptoms may be difficult to assess and progression can be insidious and is often under-appreciated. Lumbar puncture with opening pressure is a preferred method for assessing the degree of pressure elevation. Shunting procedures may be beneficial.[1]

Another recognized complication is spinal cord compression, which can result from thickening of the dura and subluxation of vertebrae.

ShuntingCredit: Illustration courtesy of the National MPS Society

Spinal cord compression

Progressive compression of the spinal cord with resulting cervical myelopathy due to thickening of the dura (hypertrophic pachymeningitis cervicalis) is common in attenuated MPS I and patients may present initially with reduced activities and exercise tolerance. This complication may not be recognized until it has progressed to the point of irreversible injury.[6]

Spinal Cord CompressionCredit: Illustration courtesy of the National MPS Society

References

  1. National MPS Society. Otitis Media: Ear Infections. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/  Accessed January 6, 2006.
  2. Clarke, L.A. Clinical diagnosis of lysosomal storage diseases. In: Organelle Diseases: Clinical Features, Diagnosis, Pathogenesis and Management. Applegarth, D.A., Dimmick, J.E., and Hall, J.G. eds. London: Chapman and Hall Medical; 1997; 46.
  3. Wraith, J.E., and Alani S.M. Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders. Arch Dis Child. 1990; 65:962-963.
  4. Haddad, F.S., Jones, D.H., Vellodi, A., Kane, N., and Pitt, M.C. (1997) Carpal tunnel syndrome in the mucopolysaccharidoses and the mucolipidoses. J Bone Joint Surg Br. 1997; 79:578.
  5. Van Heest, A.E., House J., Krivit, W., and Walker, K. Surgical treatment of carpal tunnel syndrome and trigger digits in children with mucopolysaccharide storage disorders. J Hand Surg Am. 1998; 23:239-241.
  6. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, et al, editors. The Metabolic and Molecular Bases of Inherited Disease. Vol. III. 8th ed. New York: McGraw-Hill; 2001:3427-3452.
  7. National MPS Society. Orthopedic disorders in children with MPS/ML: A Parent’s Guide. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/ Accessed January 6, 2006.
  8. Myer, C.M.D. Airway obstruction in Hurler's syndrome - Radiographic features. Int J Pediatr Otorhinolaryngol. 1990;22:92-95.
  9. Peters, M.E., Arya, S., Langer, L.O., Gilbert, E.F., Carlson, R., and Adkins, W. Narrow trachea in mucopolysaccharidoses. Pediatr Radiol. 1985; 15:226-227.
  10. National MPS Society. Cardiac problems associated with the MPS Syndromes. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/  Accessed January 6, 2006.
  11. Stone DL, Sidransky E. Hydrops fetalis: lysosomal storage disorders in extremis. Adv Pediatric. 1999;46:409-440.