Mucolipidosis I-cell disease

Mucolipidosis type 11 (I-cell disease) Mucolipidosis type IIIA (pseudo-Hurler s)... 

Some hereditary diseases are characterized by lack of two or more lysosomal enzymes. In I-cell disease (mucolipidosis II), which resembles the Hurler syndrome, at least ten enz3mies are absent or are present at much reduced levels.The biochemical defect is the absence from the Golgi cisternae of the N-acetylglucosaminyl phosphotransferase that transfers P-GlcNAc units from UDP-GlcNAc onto mannose residues (Eq. 20-22) of glycoproteins marked for use in lysosomes. 

Glycosaminoglycans from urine and tissues of patients with I-cell disease (Mucolipidosis II) contain high levels of dermatan sulphate. The increased urinary excretion of this glycosaminoglycan could reflect an abnormal metabolism of this glycosaminoglycan in connective tissue, as shown by others in I-cell cultured fibroblasts. 

The levels of j8-D-2-acetamido-deoxyglucosidase activity in skin fibroblasts from cases of cystic fibrosis and controls have been compared. In a study of I-cell disease (mucolipidosis II) a model has been presented for the structure of the carbohydrate recognition site of fibroblast-derived )3-D-2-acetamido-2-deoxyhexosidase that may extend to the other affected hydrolases and that is responsible for specific uptake of the enzyme by fibroblasts. ... 

The term mucolipidosis was introduced to denote diseases that combined features common to both mucopolysaccharidoses and sphingolipidoses (Chapter 24). Three mucolipidoses are listed in Table 48—7. In sialidosis (mucolipidosis I, ML-I), various oligosaccharides derived from glycoproteins and certain ganglio-sides can accumulate in tissues. I-cell disease (ML-II)... 

Methylmalonic aciduria (Bi2-reslstant) Mucolipidosis II (I-cell disease) Nlemann-Plck disease Sandhoff disease... 

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. 

The isolation of kallikrein (mol. wt. 3.2 x 10 ), a protease that releases kinin from kininogen, from rat urine has been reported. Kallikrein contains five residues of 2-amino-2-deoxy-D-glucose per molecule. Excessive amounts of oligosaccharides rich in sialic acid have been detected in the urine of patients with I-cell disease or mucolipidosis, indicating that there is a deficiency of a-neuraminidase in these diseases. ... 

In addition to these two types of sialidosis, there are patients with a combined defect of neuraminidase and p-galactosidase (Wenger etal. 1978, Andria etal. 1978, OK.ADAetal. 1979), possibly caused by a common defect in the biosynthetic processing of the two enzymes (Hoogeveen etal. 1980). A neuraminidase deficiency has also been observed in patients with mucolipidosis II (I-cell disease) and mucolipidosis III (Strecker etal. 1976, Thomas etal. 1976). In these disorders, however, the neuraminidase deficiency is but one of many lysosomal hydrolase deficiencies, presumably due to a defect in the proper compart-mentalization of these enzymes (Neufeld 1974). 

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