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 female is brought by her parents to the emergency room for pain in her abdomen and left thigh. Her thigh 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?
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| 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-Sachs disease.]] |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::The patient in this vignette has Gaucher's disease, a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. The abdominal pain in this patient is caused by the accumulation of lipids in the liver and spleen which can cause painful distension of these organs. Her acute leg pain is an example of a bone crisis caused by Gaucher's disease. In these episodes, buildup of lipids in the bone marrow compromises blood flow to the bone and causes very severe pain that lasts for hours to weeks. In some bone crises, ischemia of the affected region may cause tissue death and lead to fractures.
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. It is caused by deficiency of glucocerebrosidase, whose normal function is to catalyze the breakdown of glucosylceramide, a cell membrane constituent of red and white blood cells. The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into Gaucher cells, which appear on light microscopy to resemble crumpled-up paper. The disorder is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Tissue paper macrophages, WBRKeyword::Gaucher’s disease, WBRKeyword::Genetics, WBRKeyword::Sphingolipidosis, WBRKeyword::Lysosomal storage disease, WBRKeyword::Metabolism, WBRKeyword::Lipids |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |