WBR0097
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics, MainCategory::Histology |
| Sub Category | SubCategory::Hematology |
| Prompt | [[Prompt::A 3-week-old newborn is brought into the pediatric emergency department by his mother for colic and the appearance of jaundice for the past several days. On physical exam, the child’s spleen is readily palpable. Laboratory values reveal hyperbilirubinemia, and decreased RBC count. A blood smear from the child is shown below. Which of the following is the most likely cause of this child’s condition?
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| Answer A | AnswerA::Mutation of glutamic acid to valine in the beta globin gene |
| Answer A Explanation | [[AnswerAExp::A missense mutation of the sixth amino acid of the beta-globin gene to valine causes sickle cell anemia. Beta-globin mutations are not associated with Hereditary spherocytosis.]] |
| Answer B | AnswerB::Mutation of three copies of the alpha-globin gene |
| Answer B Explanation | [[AnswerBExp::Mutation of three copies of the alpha-globin gene would cause the Hemoglin H disease variant of alpha thalassemia.]] |
| Answer C | AnswerC::Mutation of ankyrin |
| Answer C Explanation | [[AnswerCExp::Ankyrin mutations are the most common genetic lesion of hereditary spherocytosis. Ankyrin normally serves as the binding partner for spectrin that allows spectrin to be incorporated into cell membranes. Ankyrin deficiency therefore causes a decrease in spectrin localization to the RBC membrane.]] |
| Answer D | AnswerD::Mutation of spectryin |
| Answer D Explanation | [[AnswerDExp::Spectrin deficiency is common to all forms of hereditary spherocytosis. However, spectrin deficiency is more often secondary to ankyrin mutations than to spectrin mutations.]] |
| Answer E | AnswerE::Nonsense mutation in the beta-globin gene |
| Answer E Explanation | [[AnswerEExp::Nonsense mutations of the beta-globin gene cause beta-thalassemia. A missense mutation of the sixth amino acid of the beta-globin gene to valine causes sickle cell anemia. Beta-globin mutations are not associated with Hereditary spherocytosis.]] |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::The patient in this vignette is most likely suffering from hereditary spherocytosis. Hereditary sphereocytosis is an autosomal dominant condition that causes an hemolytic anemia. It is characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped (donut-shaped), and therefore more prone to hemolysis. These patients will have a microcytic anemia with an increased mean corpuscular hemoglobin concentration (MCHC). On blood smear, Howell-Jolly bodies may be seen within red blood cells. Signs and symptoms include anemia, jaundice, and an enlarged spleen (splenomegaly). Acute cases can cause hypoxia through anemia and acute kernicterus through hyperbilirubinemia, particularly in newborns. Most cases can be detected soon after birth. The number of immature red blood cells (reticulocyte count) will be elevated. Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other erythrocyte membrane proteins. Mutations in ankyrin are the most common and are expected to account for between 35 to 65 percent of patients.
The most common diagnostic test for hereditary spherocytosis is the osmotic fragility test. Patients with hereditary spherocytosis tend to have acute exacerbation of the disease with viral infection. In particular, these patients may develop aplastic anemia with Parvovirus B19 infection. Eber SW, Gonzalez JM, Lux ML, et al. Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. Nat Genet. 1996;13(2):214-8.]] |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Hematology, WBRKeyword::Genetics, WBRKeyword::Hereditary spherocytosis, WBRKeyword::Spherocytosis, WBRKeyword::RBC, WBRKeyword::WJG |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |