A 3-month-old girl shows coarse facial features and increased serum activity of lysosomal enzymes. What biochemical pathway is most likely affected?

• A. Addition of mannose phosphate to lysosomal enzymes
• B. Degradation of dermatan sulfate
• C. Lysosomal acid lipase
• D. Lysosomal trafficking of exogenous cholesterol

Answer: (A)

The situation presented involves a 3-month-old girl with coarse facial features and increased serum activity of lysosomal enzymes. These clinical findings suggest a lysosomal storage disorder, which is often associated with a failure in the proper functioning of lysosomal enzymes due to issues with their trafficking or processing.

The correct response indicates that the biochemical pathway most likely affected is the addition of mannose phosphate to lysosomal enzymes. This process is critical for the proper targeting of enzymes to the lysosome. In normal physiology, lysosomal enzymes are synthesized in the endoplasmic reticulum and then processed in the Golgi apparatus, where they receive mannose-6-phosphate (M6P) tags. These tags are essential for their recognition and transport to the lysosome. When there is a defect in M6P tagging, the enzymes may be secreted into the bloodstream instead of being delivered to the lysosome, leading to increased serum activity of these enzymes and a deficiency of active enzymes within the lysosome.

This condition can be exemplified in certain lysosomal storage diseases, such as I-cell disease (mucolipidosis type II), where there is a defect in the enzyme responsible for the phosphorylation of mannose residues on lysosomal enzymes. This results in the