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تسجيل

A Loss of Glycosylation: Mucolipidosis II or I-Cell Disease

المؤلف:  Cohn, R. D., Scherer, S. W., & Hamosh, A.

المصدر:  Thompson & Thompson Genetics and Genomics in Medicine

الجزء والصفحة:  9th E, P258

2026-01-03

651

Some proteins have information contained in their primary amino acid sequence that directs them to their subcellular residence, whereas others are localized on the basis of posttranslational modifications. This latter mechanism is true of the acid hydrolases found in lysosomes, but this form of cellular trafficking was unrecognized until the discovery of I-cell disease, a severe autosomal recessive lysosomal storage disease. The dis order has a range of phenotypic effects involving facial features, skeletal changes, growth retardation, and intellectual disability and survival of less than 10 years. The cytoplasm of cultured skin fibroblasts from individuals with I-cell disease contains numerous abnormal lysosomes, or inclusions (hence the term inclusion [I] cells).

In I-cell disease, the cellular levels of many lysosomal acid hydrolases are greatly diminished, and instead they are found in excess in body fluids, including blood. This unusual situation arises because the hydrolases in these patients have not been properly modified posttranslationally. A typical hydrolase is a glycoprotein, the sugar moiety containing mannose residues, some of which are phosphorylated. The mannose-6-phosphate residues are essential for recognition of the hydrolases by receptors on the cell and lysosomal membrane surface. In I-cell disease there is a defect in the enzyme that transfers a phosphate group to the mannose residues. The fact that many enzymes are affected is consistent with the diversity of clinical abnormalities seen in these patients.