Choose the ONE best answer.
4.1. Mucopolysaccharidoses are hereditary lysosomal storage diseases. They are caused by:
A. defects in the degradation of glycosaminoglycans.
B. defects in the targeting of enzymes to lysosomes.
C. an increased rate of synthesis of the carbohydrate component of proteoglycans.
D. an insufficient rate of synthesis of proteolytic enzymes.
E. the synthesis of abnormally small amounts of core proteins.
F. the synthesis of heteropolysaccharides with an altered structure.
Correct answer = A. The mucopolysaccharidoses are caused by deficiencies in any one of the lysosomal acid hydrolases responsible for the degradation of glycosaminoglycans (not proteins). The enzyme is correctly targeted to the lysosome, so blood levels of the enzyme do not increase, but it is nonfunctional. In these diseases, synthesis of the protein and carbohydrate components of proteoglycans is unaffected, in terms of both structure and amount.
4.2. The presence of the following compound in the urine of a patient suggests a deficiency in which one of the enzymes listed below?
A. Galactosidase
B. Glucuronidase
C. Iduronidase
D. Mannosidase
E. Sulfatase
Correct answer = E. Degradation of glycoproteins follows the rule: last on, first off. Because sulfation is the last step in the synthesis of this sequence, a sulfatase is required for the next step in the degradation of the compound shown.
4.3. An 8-month-old boy with coarse facial features, skeletal abnormalities, and delays in both growth and development is diagnosed with I-cell disease based on his presentation and on histologic and biochemical testing. I-Cell disease is characterized by:
A. decreased production of cell surface O-linked glycoproteins.
B. elevated levels of acid hydrolases in the blood.
C. inability to N-glycosylate proteins.
D. increased synthesis of proteoglycans.
E. oligosaccharides in the urine.
Correct answer = B. I-Cell disease is a lysosomal storage disease caused by deficiency of the phosphotransferase needed for synthesis of the mannose 6phosphate signal that targets acid hydrolases to the lysosomal matrix. This results in secretion of these enzymes from the cell and accumulation of materials within the lysosome because of impaired degradation. None of the other choices relates to I-cell disease or lysosomal function. Oligosaccharides in the urine are characteristic of the muco-and polysaccharidoses but not I-cell disease (a type II mucolipidosis).
4.4. An infant with corneal clouding has dermatan sulfate and heparan sulfate in his urine. Decreased activity of which of the enzymes listed below would confirm the suspected diagnosis of Hurler syndrome?
A. α-L-Iduronidase
B. α-Glucuronidase
C. Glycosyltransferase
D. Iduronate sulfatase
Correct answer = A. Hurler syndrome, a defect in the lysosomal degradation of glycosaminoglycans (GAG) with corneal clouding, is due to a deficiency in αL-iduronidase. β-Glucuronidase is deficient in Sly syndrome, and iduronate sulfatase is deficient in Hunter syndrome. Glycosyltransferases are enzymes of GAG synthesis.
4.5. Distinguish between glycoproteins and proteoglycans.