Pseudo-Hurler polydystrophy

Pseudo-Hurler polydystrophy is another genetic disease closely related to I-ceU disease. It is a milder condition, and patients may survive to adulthood. Smdies have revealed that the GlcNAc phosphotransferase involved in I-cell disease has several domains, including a catalytic domain and a domain that specifi-... 

Several disorders that lead to Impaired lysosome function Include the mucolipidoses l-cell disease and pseudo-Hurler polydystrophy. 

Pseudo-Hurler polydystrophy (mucolipidosis III, ML-III) is related to l-cell disease, but cells of these patients retain some activity of the deficient enzyme. 

The answer is D. As this patient ages, a variety of skeletal defects and short stature that are consistent with a lysosomal storage disease (mucolipidosis), either I-cell disease or pseudo-Hurler polydystrophy, are developing. Both diseases arise from a deficiency of an enzyme involved in synthesis of the Man-6-P marker on lysosomal enzymes. Such misaddressed proteins are secreted rather than trafficked to the lysosomes. The degradative function of lysosomes is impaired as a result and the organelles tend to accumulate waste products (hence, the term storage disease ). It is these inclusion bodies or dense structures that would be visible by microscopic examination of the patient s cells in a biopsy specimen. 

Komfeld, S., and Sly, W. S. (1995) I-Cell Disease and Pseudo-Hurler Polydystrophy Disorders of Lysosomal Enzyme Phosphorylation and Localization, in The Metabolic and Molecular Bases of Inherited Disease, 7th ed., ed. C. R. Scriver A. L. Beaudet, W S. Sly, and D. Valle, McGraw-Hill, New York, pp.2495-2508. 

Table 17-1. Lysosomal Enzyme Activities in Serum from Patients with I-Cell Disease and Pseudo-Hurler Polydystrophy ...

It is widely believed that I-cell disease (ML-II) and pseudo-Hurler polydystrophy (ML-III) are variants of the same disorder because fibroblasts from both these disorders are deficient in phosphotransferase activity. At the molecular level, the primary and most significant difference is that in I-cell disease the deficiency is essentially total, whereas in pseudo-Hurler polydystrophy there appears to be significant residual activity (approximately 10% of control values). The molecular basis for these two diseases may, however, be distinct, as evidenced by genetic complementation studies demonstrating complementation of ML-II by some ML-III fibroblasts (Mueller et al., 1983). Although two clinical presentations of I-cell disease have been described (i.e., the neonate and 6- to 12-month-old patient), correlation of the degree of deficiency of phosphotransferase activity with clinical severity in the two I-cell disease presentations remains controversial. 

The I-cell patient has proved invaluable for elucidation of the complex nature of intracellular packaging and sorting of lysosomal enzymes. The physiological importance of this signal-mediated pathway is evident in that fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy secrete rather than target most of their lysosomal enzymes. Thus, the molecular theme of I-cell disease is that of faulty lysosomal targeting, the inability to transport (i.e., sort) lysosomal enzymes from their site of synthesis to the lysosome. 

Although both I-cell disease and pseudo-Hurler polydystrophy patients are deficient in phosphotransferase activity, they exhibit different patterns of intracellular and extracellular... 

Ben-Yoseph Y, Pack BA, Mitchell DA, et al. Characterization of the mutant A -acetylglucosaminyl-phosphotransferase in I-cell disease and pseudo-Hurler polydystrophy complementation analysis and kinetic studies. Enzyme 35 106-116,1986. 

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