Nervous System

Individuals with severe MPS I suffer progressive and profound cognitive impairment, in contrast to patients with attenuated forms of the disease.[1]

The exact mechanisms for cognitive impairment are complex and may involve neuron loss with atrophy, altered neuronal structure and the effects of communicating hydrocephalus. Early development may be normal but developmental delay is usually suspected by 12 months.[1] Thereafter, there is progressive deterioration and by 18 months, developmental delay is usually apparent. From this point on most patients do not progress in development but plateau for a number of years followed by a slow decline in intellectual capabilities. By the time of death, most patients are severely mentally impaired.

There is extreme heterogeneity in intellectual manifestations exhibited by individuals with attenuated forms of MPS I disease. Here intellectual involvement may range from little or no intellectual dysfunction to exhibiting a more protracted course compared to severe patients.

Structural CNS manifestations

In addition to the direct CNS effects, communicating high-pressure hydrocephalus is common in MPS I patients. The obstruction to resorption of cerebrospinal fluid by arachnoid villi causes an associated increase in intracranial pressure, leading to brain compression. Rapidly increasing pressure can be the cause of rapid developmental decline in some patients. Symptoms may be difficult to assess and progression can be insidious and is often underappreciated. Papilledema as an indicator may not be reliable sign of increased intracranial pressure.[1] MRI can show ventriculomegaly, but often imaging studies cannot reliably distinguish between atrophy and brain compression in MPS I. Lumbar puncture with opening pressure is a preferred method for assessing the degree of pressure elevation. Shunting procedures may be beneficial for most children.[2]

Peripheral nervous system

Carpal tunnel syndrome is common in patients with attenuated MPS I. Most patients lack typical symptoms (pain, tingling or numbness) until severe compression occurs, even when there were florid signs and severe neurophysiological deficits.[3],[4],[5] Surgical decompression of the median nerve results in complete restoration of motor hand activity in some patients and partial improvement in others.[5],[6] Intervention at an early stage of involvement, prior to severe nerve damage is recommended. [1] Hypertrophic pachymeningitis cervicalis as well as spinal cord compression at any level should be aggressively and quickly evaluated in patients with attenuated MPS I. Early surgical intervention may prevent severe complications.

Next: Skeletal System

References:

  1. Clarke, L.A. (1997) 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.). Chapman and Hall Medical, London, p. 37.
  2. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135. Accessed April 11, 2017.
  3. Wraith, J.E., and Alani, S.M. (1990) Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders. Arch Dis Child. 65: 962.
  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. 79: 576.
  5. Van Heest, A.E., House J., Krivit, W., and Walker, K. (1998) Surgical treatment of carpal tunnel syndrome and trigger digits in children with mucopolysaccharide storage disorders. J Hand Surg (Am). 23: 236.
  6. Pronicka, E., Tylki-Szymanska, A., Kwast, O., Chmielik, J., Maciejko, D., and Cedro A. (1988). Carpal tunnel syndrome in children with mucopolysaccharidoses: Needs for surgical tendons and median nerve release. J Ment Defic Res. 32: 79.