WBR0318

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Serge Korjian, Yazan Daaboul, and Alison Leibowitz [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 6-month-old boy is brought by his mother to the physician's office for failure to thrive. Following appropriate work-up, the patient is diagnosed with a disease that is characterized by an inability to phosphorylate mannose residues on glycoproteins and results in the aggregation of a variety of substrates in the extracellular matrix. Which of the following clinical features are associated with this patient's condition?]]
Answer A	AnswerA::Clouded corneas and restricted joint movement
Answer A Explanation	AnswerAExp::The most common clinical features of inclusion cell disease are clouded corneas and restricted joint movement.
Answer B	AnswerB::Partial albinism and peripheral neuropathy
Answer B Explanation	AnswerBExp::Chediak-Higashi syndrome is a disease characterized by peripheral neuropathy, peripheral neuropathy, and pyogenic infections. Chediak-Higashi syndrome occurs as a result of a mutation in the lysosomal trafficking regulator gene.
Answer C	AnswerC::Situs inversus and bronchiectasis
Answer C Explanation	AnswerCExp::Kartagener's syndrome or primary ciliary dyskinesia is caused by a dynein arm defect. It is characterized by infertility, bronchiectasis, and sinusitis. It is often associated with situs inversus.
Answer D	AnswerD::Thymic aplasia and recurrent infections
Answer D Explanation	AnswerDExp::Severe combined immunodeficiency (SCID) is characterized by thymic aplasia and recurrent infections (bacterial, viral, fungal, and protozoal). SCID commonly results from a defective interleukin-2 receptor or adenosine deaminase deficiency.
Answer E	AnswerE::Hepatomegaly and aseptic necrosis of the femur
Answer E Explanation	AnswerEExp::Gaucher's disease, a lysosomal storage disease, is characterized by hepatomegaly and aseptic necrosis of the femur. On pathology, Gaucher's cells ("crumpled tissue paper" macrophages) are observed.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Inclusion cell disease or I-cell disease (mucolipidosis type II) is a lysosomal storage disease characterized by a defective phosphorylation of mannose residues due to a defect of GlcNAc-phosphotransferase, which is normally found on the Golgi apparatus. Consequently, lysosomal enzymes are secreted out of the cell, rather than being directed into the lysosomes, resulting in vacuolization of the cytoplasm due to the accumulation of substances that would normally be degraded by the lysozomal enzymes. Typical manifestations of inclusion cell disease are coarse facial features, restricted joint movement, and clouded corneas among very young children, all of which result from the aggregation of substances that would otherwise normally be degraded in the lysosomes. I-cell disease is usually deadly in early childhood. Educational Objective: Clinical features of inclusion cell disease (I-cell disease) are coarse facial features, clouded corneas, and restricted joint movement, all of which result from the aggregation of substances in the cytoplasm that would otherwise be normally degraded in the lysosomes. References: Tiede S, Storch S, Lübke T, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med. 2005;11(10):1109-12. First Aid 2015 page 73 First Aid 2014 page 77]]
Approved	Approved::Yes
Keyword	WBRKeyword::I-cell disease, WBRKeyword::Inclusion cell disease, WBRKeyword::Mannose-6-phophase, WBRKeyword::Lysosome, WBRKeyword::Lysosomal storage disease, WBRKeyword::Mucolipidosis
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