A 6-month-old boy is brought to his pediatrician by his mother for a follow-up examination. When born, the infant had a low birth weight, coarse facial features, and restricted motion of the extremities. Serum and urine analysis at this time indicated the presence of lysosomal enzyme activity. Physical examination today shows psychomotor retardation and hepatomegaly. A biopsy of skin is taken and analysis of the fibroblasts indicates that they contain multiple intracellular cytoplasmic inclusions. A deficiency in which of the following posttranslational modifications is most likely present in this infant?

Question

Quizplus · Accepted Answer

The infant's symptoms and findings are consistent with I-cell disease, which is caused by a deficiency in the phosphorylation of mannose residues on lysosomal enzymes. This modification is necessary for the proper targeting of enzymes to the lysosome.  Enzymes that are destined for the lysosomes (lysosomal enzymes) are directed there by the presence of mannose-6-phosphate residues in these enzymes. A specific Man-6-P receptor (MPR) is present in the membranes of the Golgi apparatus. Binding of Man-6-P to this receptor targets proteins to the lysosomes. Lack of this modification results in increased levels of lysosomal enzymes in the blood and urine.

A 6-Month-Old Boy Is Brought to His Pediatrician by His