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Hereditary Spherocytosis

Hereditary Spherocytosis is a topic covered in the 5-Minute Pediatric Consult.

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Basics

Description

  • Hereditary spherocytosis (HS) is the most common red blood cell (RBC) membrane disorder causing hemolytic anemia.
  • Hemolytic anemia with shortened RBC lifespan due to an inherent defect in RBC membrane proteins leading to selective destruction of RBCs in the spleen
  • Gradual membrane loss with preserved intracellular volume results in spherocytosis with decreased RBC deformability and increased osmotic fragility.
  • Pathophysiologically related to hereditary elliptocytosis and hereditary ovalocytosis
  • Severity related to degree of membrane loss
    • Mild (20% of patients)
      • Hemoglobin near normal
      • Slight reticulocytosis (<6%)
      • Compensated hemolysis, mild splenomegaly
      • Often not diagnosed until adulthood due to gallstones
    • Moderate (60% of patients)
      • Hemoglobin 8 to 12 mg/dL
      • Reticulocytes generally >6%
      • >50% patients have splenomegaly.
    • Moderately severe (10%)
      • Hemoglobin 6 to 8 mg/dL
      • Reticulocytes >10%
      • Intermittent transfusions
    • Severe (3–5%)
      • Life-threatening anemia requiring regular transfusions
      • Almost always recessive

Epidemiology

Most common inherited anemia in individuals of Northern European descent (~1:2,500)

Risk Factors

Genetics

  • ~75% of cases are inherited in an autosomal dominant pattern.
  • The other 25% are autosomal recessive forms, dominant disease with reduced penetrance, or new mutations.

Pathophysiology

  • The most common abnormality is a deficiency of ankyrin and subsequent decrease in spectrin, two major proteins of the erythrocyte membrane skeleton (50–60% Northern European descent; 5–10% Japan).
    • Spectrin deficiency alone accounts for 20% of HS.
    • Mutations in other erythrocyte surface proteins also occur, including the following:
      • β-Spectrin (typically mild to moderately severe), α-spectrin (severe HS)
      • Band 3 (15–20% generally mild to moderately severe)
      • Protein 4.2 (<5% HS, recessive and results in almost complete absence)
      • Rh antigen (<10% mild to moderate hemolytic anemia)
  • The membrane skeletal defect causes RBC membrane fragility, resulting in membrane loss.
  • The sequelae are as follows:
    • Loss of cell surface area relative to volume (spherocytosis) causes a decrease in cellular deformability.
    • The spleen detains and “conditions” the nondeformable spherocytic RBC.
    • Conditioning of cells involves depletion of adenosine 5’-triphosphate (ATP), increased glycolysis, increased influx and efflux of sodium, and loss of membrane lipid.
  • Ultimately, these events lead to premature RBC destruction.

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Citation

Cabana, Michael D., editor. "Hereditary Spherocytosis." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617512/all/Hereditary_Spherocytosis.
Hereditary Spherocytosis. In: Cabana MD, ed. 5-Minute Pediatric Consult. 8th ed. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617512/all/Hereditary_Spherocytosis. Accessed April 18, 2019.
Hereditary Spherocytosis. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult. Available from https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617512/all/Hereditary_Spherocytosis
Hereditary Spherocytosis [Internet]. In: Cabana MD, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2019 April 18]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617512/all/Hereditary_Spherocytosis.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Hereditary Spherocytosis ID - 617512 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617512/all/Hereditary_Spherocytosis PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -