Foundations · Year 1 · from Foundations
Case 1: Sickle Cell Disease (Protein Misfolding)
Clinical Image
Source: Wikipedia - Sickle cell disease - Public Domain
Case Presentation
A 19-year-old African American male presents to the emergency department with severe pain in his lower back, chest, and bilateral legs for the past 8 hours. He has a known history of sickle cell disease (HbSS). Vital signs show temperature 38.2C, heart rate 110, blood pressure 130/85, respiratory rate 22, and oxygen saturation 92% on room air. Physical examination reveals pallor, scleral icterus, and diffuse tenderness over the spine and extremities without swelling or erythema. Laboratory studies show hemoglobin 7.2 g/dL (baseline 8.5), reticulocyte count 12%, total bilirubin 4.2 mg/dL, and LDH 450 U/L. Peripheral blood smear shows sickle-shaped erythrocytes. The patient is experiencing an acute vaso-occlusive crisis. Treatment includes IV fluids, supplemental oxygen, and opioid analgesia. He is started on hydroxyurea for crisis prevention and counseled about triggers including dehydration, cold exposure, and high altitude.
Key Learning Points
- Sickle cell disease results from a single amino acid substitution (Glu6Val) in beta-globin that causes hemoglobin polymerization under low oxygen conditions
- This missense mutation changes the protein's quaternary structure, creating hydrophobic patches that promote aggregation into rigid fibers
- The clinical manifestations (vaso-occlusion, hemolysis, organ damage) all stem from the altered physical properties of the mutant hemoglobin