• Clinical science

Hereditary spherocytosis

Abstract

Hereditary spherocytosis (HS) is the most common congenital hemolytic disorder among individuals of northern European descent. In most cases, it is an autosomal dominant disease that is caused by red blood cell (RBC) membrane protein defects, which render the RBCs more vulnerable to osmotic stress and hemolysis. Clinical presentation ranges from mild HS, which is generally asymptomatic, to severe HS, which can already present in utero with hydrops fetalis. Moderate HS, which is the most common form, usually presents in infancy or childhood with the classic triad of anemia, jaundice, and splenomegaly. Diagnosis is established based on family history, typical laboratory findings (e.g., elevated mean corpuscular hemoglobin concentration and RBC distribution width), and tests (e.g., eosin-5-maleimide binding test, osmotic fragility test). Treatment depends on the severity of the disease and involves acute measures (e.g., red blood cell transfusions, phototherapy), medication (e.g., folic acid supplementation), and splenectomy. HS patients are also at risk for complications such as hemolytic and aplastic crises, megaloblastic anemia, and gallstone formation.

Epidemiology

  • Incidence: 1/5000 in the US
  • Most common inherited hemolytic disease among individuals of Northern European descent

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[2][1]

Pathophysiology

Genetic mutation → Defects in RBC membrane proteins (especially spectrin and/or ankyrin); responsible for tying the inner membrane skeleton with the outer lipid bilayer → Continuous loss of lipid bilayer components → Decreased surface area of RBCs in relation to volume Sphere-shaped RBCs with decreased membrane stability → Inability to change form while going through narrowed vessels:

References:[3][4]

Clinical features

  • Presentation is variable.
    • Mild HS (20–30% of cases): often asymptomatic
    • Moderate HS (60–75% of cases): onset of symptoms in infancy or childhood
    • Severe HS (5% of cases): onset of symptoms in newborns or even in utero (hydrops fetalis)
  • Anemia and pallor
  • Jaundice (due to unconjugated bilirubin)
  • Splenomegaly with left upper quadrant pain
  • Black pigment gallstones (made of calcium bilirubinate), may lead to cholecystitis

References:[5][1][6][7]

Diagnostics

References:[2][1][4][8][9][10]

Treatment

References:[1]

Complications

References:[11][9]

We list the most important complications. The selection is not exhaustive.