MPS I Disease

Mucopolysaccharidosis I (MPS I) is a rare, autosomal recessive disease with pathologic manifestations in multiple organ systems and tissues. The disease is caused by a defect in the gene coding for the lysosomal enzyme alpha-L-iduronidase; as a result, the cells of affected individuals either are unable to produce the enzyme or produce it in low amounts. This results in an inability of the lysosome to effect the stepwise degradation of certain glycosaminoglycans (GAGs) - namely dermatan sulfate and heparan sulfate - a process essential for normal growth and homeostasis of tissues^{[1, 2]}. These glycosaminoglycans, which are important constituents of the extracellular matrix, joint fluid, and connective tissue throughout the body, progressively accumulate in the lysosome, ultimately causing cell, tissue, and organ dysfunction by largely unknown pathophysiological mechanisms.

MPSI is considered to be the prototypical lysosomal storage disorder with progressive multi-systemic disease and presenting features that vary depending on where a patient is on the disease continuum.

The historical classifications of MPS I, Hurler, Hurler-Scheie and Scheie syndromes do not adequately reflect the tremendous variation in clinical symptoms. The manifestations seen with each classification are not mutually distinct and often overlap. Therefore the disease is best characterized as alpha-L-iduronidase deficiency with or without CNS involvement.

References

1. 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.

2. Clarke LA. Clinical diagnosis of lysosomal storage diseases. In: Organelle Diseases. Clinical Features, Diagnosis, Pathogenesis and Management. Applegarth DA, Dimmick JE, Hall JG, editors. London: Chapman and Hall Medical; 1997. p. 45-8.