WBR0124

Author	[[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry, MainCategory::Genetics, MainCategory::Histology
Sub Category	SubCategory::Cardiology, SubCategory::Hematology
Prompt	[[Prompt::A 9 year old girl is brought by her parents to the emergency room for abdominal pain and pain in her left thigh. The pain developed over the past several days, and today she was unable to walk because of it. She has a history of anorexia and abdominal bloating for the past several years. She recalls one previous incident of pain in her thigh. On physical exam, the abdomen is distended, the spleen is palpable 4 cm below the costal margin and the liver is tender to mild palpation. The left thigh retains full range of motion, but is painful with knee extension and deep palpation. There is no family history of sickle cell anemia/trait and the patient tests negative for HbS by hemoglobin electrophoresis. Peripheral blood smear reveals marked microcytosis with anisocytosis. Bone marrow biopsy confirms the diagnosis with the visualization of “tissue paper” macrophages pictured below. Which of the following is the most likely underlying genetic lesion in this patient? ]]
Answer A	AnswerA::Mutation in HFE
Answer A Explanation	[[AnswerAExp::HFE gene is mutated in hereditary hemochromatosis.]]
Answer B	AnswerB::Deficiency of glucocerobrosidase
Answer B Explanation	[[AnswerBExp::Glucocerobrosidase is the mutated gene in Gaucher’s disease.]]
Answer C	AnswerC::Deficiency of galactocerebrosidase
Answer C Explanation	[[AnswerCExp::Galactocerebrosidase gene is mutated in Krabbe’s disease.]]
Answer D	AnswerD::Deficiency of alpha-galactosidase A
Answer D Explanation	[[AnswerDExp::Alpha-galactosidase A gene is mutated in Fabry’s disease.]]
Answer E	[[AnswerE::Deficiency of hexosaminidase A]]
Answer E Explanation	[[AnswerEExp::Hexosaminidase A gene is mutated in Tay-Sach’s disease.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids. The disorder is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. Educational Objective: Gaucher's disease is caused by a deficiency of glucocerebrosidase. References: First Aid page 114; First Aid 2012 page 116]]
Approved	Approved::Yes
Keyword	WBRKeyword::Tissue paper macrophages, WBRKeyword::Gaucher’s disease
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::