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Medical Emergencies · patient case with 2 questions

A painful crisis in a young adult

demo: 24-year-old male

chief: Severe generalised bone pain, worst in the mandible and long bones, for two days.

history: Sickle cell anaemia diagnosed in infancy. Two hospital admissions in the past year for painful crises. He became dehydrated at a football match the day before this episode began.

meds: Hydroxyurea, folic acid.

findings: Afebrile, tachycardic. Panoramic radiograph shows a stepladder trabecular pattern with enlarged marrow spaces and generalised radiolucency of the jaws.

Question 1

Sickle cell anaemia results from which type of mutation?

  1. Frameshift deletion
  2. Silent (same-sense) mutation
  3. Missense mutation
  4. Nonsense mutation
Show answer and explanation

Correct answer: C. Missense mutation

  • A. A frameshift results from insertion or deletion of a number of bases not divisible by three, scrambling everything downstream. The sickle mutation is a clean single substitution.
  • B. A silent mutation changes the base but not the encoded amino acid, thanks to codon redundancy, so it produces no phenotype.
  • C. Correct. A single base substitution of adenine for thymine in the sixth codon of the beta-globin gene replaces glutamic acid with valine. One amino acid is exchanged for a different one, which is the definition of a missense mutation. Losing that negative charge lets deoxygenated haemoglobin S polymerise.
  • D. A nonsense mutation converts a codon into a stop codon and truncates the protein. Some beta-thalassaemia alleles arise this way, but sickle cell disease does not.

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Question 2

Which change to the sickled erythrocyte contributes most directly to the anaemia and to vaso-occlusive crisis?

  1. A markedly shortened red cell lifespan
  2. Increased affinity of haemoglobin for oxygen
  3. Increased red cell deformability
  4. A prolonged red cell half life
Show answer and explanation

Correct answer: A. A markedly shortened red cell lifespan

  • A. Correct. Polymerised haemoglobin S distorts the cell into a rigid sickle. Those cells are cleared by the spleen and haemolyse in the circulation, cutting the normal 120-day lifespan to roughly 10 to 20 days. The rigid cells also jam in the microvasculature, which is the vaso-occlusion that causes the pain.
  • B. Haemoglobin S has reduced oxygen affinity, shifting the dissociation curve to the right. In any case increased affinity would not drive the sickling process; deoxygenation does.
  • C. Sickled cells are less deformable, not more. Loss of the flexibility that lets a normal biconcave disc squeeze through a capillary is precisely why they occlude vessels.
  • D. The opposite is true. Any process that lengthened red cell survival would improve, not worsen, the anaemia.

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