Spherocytosis

Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia in people of Northern European descent. It is caused by mutations in genes encoding red blood cell membrane proteins, most often ankyrin (ANK1), but also spectrin (SPTA1, SPTB), band 3 (SLC4A1), and protein 4.2 (EPB42). These defects weaken the vertical interactions that attach the membrane to the cytoskeleton.

As a result, red blood cells lose membrane surface area but retain contents, becoming small, spherical, and less deformable. They are preferentially destroyed in the spleen, leading to extravascular hemolysis. The mean corpuscular hemoglobin concentration (MCHC) is often increased, and the red cell lifespan is shortened (roughly 10–20 days).

Clinical features include mild to moderate anemia, jaundice, splenomegaly, and pigmented gallstones. Neonatal jaundice is common. Aplastic crises can occur with parvovirus B19 infection. Some patients have only mild symptoms; others have significant anemia requiring therapy.

Diagnosis relies on blood smear showing spherocytes, increased MCHC, and reticulocytosis. Osmotic fragility testing and eosin-5'-maleimide (EMA) binding by flow cytometry are commonly used. Genetic testing can confirm mutations and guide family counseling.

Management includes folic acid supplementation and routine monitoring. Splenectomy, usually deferred until after age five, reduces hemolysis and improves anemia in severe cases but increases the risk of overwhelming postsplenectomy infection; appropriate vaccinations and, in some settings, antibiotic prophylaxis are recommended. The prognosis is generally favorable with treatment; splenectomy improves hemoglobin but does not cure the underlying membrane defect, and gallstone risk persists.