WBR0318

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
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, that patient is diagnosed with a disease that is characterized by an inability to phosphorylate mannose residues on glycoproteins, leading to the aggregation of a variety of substrates in the extracellular matrix. Which of the following clinical features are most likely to be present in this patient?]]
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 the 3Ps: Peripheral neuropathy, Peripheral neuropathy, and Pyogenic infections. Chediak-Higashi syndrome occurs as a result of a lysosomal trafficking regular gene mutation.]]
Answer C	AnswerC::Situs inversus and bronchiectasis
Answer C Explanation	AnswerCExp::Kartagener's syndrome or primary ciliary dyskinesia is often characterized by infertility, bronchiectasis, sinusitis, and is often associated with situs inversus. Kartagener's syndrome occurs as a result of a dynein arm defect.
Answer D	AnswerD::Thymic aplasia and recurrent infections
Answer D Explanation	AnswerDExp::Severe combined immunodeficiency is often characterized by thymic aplasia and recurrent infections (bacterial, viral, fungal, and protozoal). It occurs as a result of 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 often 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::The patient in this scenario is most likely presenting with inclusion cell disease, also known as I-cell disease (mucolipidosis type II), a lysosomal storage disease characterized by a defective phosphorylation of mannose residues. This occurs 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 to the lysosomes. This leads to vacuolization of the cytoplasm due to the accumulation of substances that would normally be degraded by the lysozomal enzymes. Typical manifestations of I-cell disease are coarse facial features, restricted joint movement, and clouded corneas in very young children, which all result from the aggregation of substances that normally would be degraded in the lysosomes. I-cell disease is usually deadly in early childhood. Educational Objective: Clinical features of I-cell disease are coarse facial features, clouded corneas, and restricted joint movement, which all result from the aggregation of substances in the cytoplasm that would normally be 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 2014 page 77]]
Approved	Approved::Yes
Keyword	WBRKeyword::Restricted, WBRKeyword::joint, WBRKeyword::movement, WBRKeyword::I-cell disease, WBRKeyword::Inclusion cell disease, WBRKeyword::Mannose-6-phophase, WBRKeyword::Lysosome, WBRKeyword::Lysosomal storage disease, WBRKeyword::Mucolipidosis
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