A 9-month-old boy is brought to the clinic for a routine follow-up. His mother is concerned because the patient is not yet able to sit up unsupported. He was born at term and has had muscle weakness since birth. Vital signs are normal. The patient is alert but has diminished tone. Examination shows a prominent forehead with a depressed nasal bridge. Eye examination shows epicanthal folds. Analysis of lysosomal acid hydrolases shows an increased concentration within the serum and a decreased level within the cultured skin fibroblast cells. This patient most likely has a defect in which of the following steps of enzyme production?

Question

A 9-month-old boy is brought to the clinic for a routine follow-up.  His mother is concerned because the patient is not yet able to sit up unsupported.  He was born at term and has had muscle weakness since birth.  Vital signs are normal.  The patient is alert but has diminished tone.  Examination shows a prominent forehead with a depressed nasal bridge.  Eye examination shows epicanthal folds.  Analysis of lysosomal acid hydrolases shows an increased concentration within the serum and a decreased level within the cultured skin fibroblast cells.  This patient most likely has a defect in which of the following steps of enzyme production?

Quizplus · Accepted Answer

11ec160b_36b2_03f4_9249_2b9b70d0f086_MD0001_00 Protein synthesis is a process involving the following steps: An error can occur at any of these stages and result in disease. Inclusion cell (I-cell) disease is a defect in posttranslational modification in the Golgi body. Normally, proteins designated for lysosomes are tagged with mannose-6-phosphate. However, in I-cell disease, a defect in a phosphotransferase enzyme prevents phosphorylation of mannose. Lysosomal acid hydrolases are therefore transported inappropriately to the extracellular space, causing an increase in serum concentration and a decrease in intracellular concentration, as seen in this patient. Without acid hydrolases to degrade cellular debris within lysosomes, the waste products (eg, mucolipids, mucopolysaccharides) accumulate and form inclusion bodies characteristic of the disease. I-cell disease presents in infancy with features similar to Hurler syndrome, including skeletal abnormalities (eg, coarse facial features), developmental delay, cloudy corneas, and recurrent respiratory infections. I-cell disease is generally fatal in childhood. (Choice A) DNA methylation silences gene transcription so that the affected protein would be completely absent. A pathologic example of DNA methylation is the inhibition of tumor suppressor genes as a mechanism for cancer development. (Choice C) A defect in protein folding, as seen with the CFTR protein in cystic fibrosis, would result in abnormal protein functioning. Protein concentration may be normal or low due to more rapid degradation of the abnormal protein. (Choices D and E) Splicing mutations can result in inappropriate removal of exons or persistence of introns; this creates aberrant mRNA that is presented for translation and results in production of an abnormal protein. Similarly, a defect in translation results in insufficient or abnormal protein synthesis, which is reflected both in the serum and intracellularly. Educational objective: Posttranslational modification of proteins is important for targeting proteins to the correct location. This step is defective in I-cell disease, which is characterized by a lack of mannose residue phosphorylation, resulting in inappropriate trafficking of acid hydrolases to the extracellular space instead of to lysosomes.

A 9-Month-Old Boy Is Brought to the Clinic for a Routine