MPS I – Nervous System

Developmental Delay and Severe Mental Retardation

Patients with MPS I manifest a wide range of intellectual involvement. Some MPS I patients will suffer progressive and profound mental retardation while others will exhibit little or no intellectual dysfunction. In severe patients, early development may be normal but developmental delay is usually suspected by 12 months^[1]. 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.

Structural CNS Manifestations

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.^[2] Another recognized complication is spinal cord compression, which can result from thickening of the dura or subluxation of vertebrae.

Peripheral Nervous System

Some patients with MPS I may have poor hand function, in part as a result of carpal tunnel syndrome (median nerve entrapment).^[3] 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)^{[4, 5, 6]}. 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.^[6]

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, pp. 37.

2. Neufeld, E.F., and Muenzer, J. (2001) The mucopolysaccharidoses. In: The Metabolic and Molecular Bases of Inherited Disease. Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W., and Vogelstein, B. (eds.). 8th edition, Vol. III. McGraw-Hill, Medical Publishing Division, pp. 3421.

3. Wraith, J.E. (1995) The mucopolysaccharidoses: A clinical review and guide to management. Arch Dis Child 72: 263.

4. Wraith, J.E., and Alani, S.M. (1990) Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders. Arch Dis Child 65: 962.

5. 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.

6. 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.