WBR0787

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian M.D. and Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Head and Neck, SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 6-month-old girl admitted to the pediatrics ward for fever was found to have coarse facial features, corneal clouding, bilateral dislocated hips, and significant developmental delay. An assay of alpha-mannosidase and beta-galactosidase, both of which are lysosomal enzymes, demonstrated deficient intracellular concentrations, but excessive plasma concentrations up to 50-fold the upper limit of normal. Which of the following processes is likely to be defective in this child?]]
Answer A	AnswerA::Ubiquitin tagging
Answer A Explanation	AnswerAExp::Ubiquitin tagging is important for protein degradation by proteasomes. It is not involved in the pathogenesis of I-cell disease.
Answer B	AnswerB::Zymogen trimming
Answer B Explanation	AnswerBExp::Zymogen trimming is a form of post-translational modification needed to produce active enzymes. It is not involved in the pathogenesis of I-cell disease.
Answer C	AnswerC::COPI trafficking
Answer C Explanation	AnswerCExp::COPI trafficking is involved in retrograde transport from the Golgi apparatus to the endoplasmic reticulum. It is not involved in the pathogenesis of I-cell disease.
Answer D	AnswerD::COPII trafficking
Answer D Explanation	AnswerDExp::COPII trafficking is involved in anterograde transport from the endoplasmic reticulum to the Golgi apparatus. It is not involved in the pathogenesis of I-cell disease.
Answer E	AnswerE::Mannose-6-phosphate tagging
Answer E Explanation	AnswerEExp::Mannose-6-phosphate tagging is important to tag enzymes to lysosomes. The process is defective among patients with I-cell disease.
Right Answer	RightAnswer::E
Explanation	[[Explanation::I-cell disease is a rare autosomal recessive lysosomal storage disorder that manifests very early in life. Clinically, it is characterized by failure to thrive, coarse facial features, corneal clouding, and limitations in joint movement with hip dislocation. The pathophysiology of I-cell disease is related to a defect in mannose-6-phosphate tagging of enzymes that are to be transported into lysosomes. Instead, lysosomal enzymes are secreted outside the cell, leading to an increase in their plasma concentrations. Treatment is usually supportive. Bone marrow transplant may be effective in some patients. Educational Objective: I-cell disease is characterized by a defect in mannose-6-phosphate tagging of lysosomal enzymes. References: Güngör N, Coşkun T, Akçören Z, Cağlar M. I-cell disease. A case report and review of the literature. Turk J Pediatr. 1994;36(2):145-52. First Aid 2015 page 73.]]
Approved	Approved::Yes
Keyword	WBRKeyword::I-cell disease, WBRKeyword::Lysosomal storage diseases, WBRKeyword::Autosomal recessive, WBRKeyword::Metabolic disorders, WBRKeyword::Inborn errors of metabolism
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::