Hereditary spherocytosis

Hereditary spherocytosis (HS), also known as Minkowski-Chauffard disease, is the most common inherited red blood cell membrane disorder, particularly among individuals of Northern European descent. It is caused by mutations in genes encoding proteins of the red blood cell membrane skeleton, including ankyrin (ANK1), band 3 protein (SLC4A1), alpha-spectrin (SPTA1), beta-spectrin (SPTB), and protein 4.2 (EPB42). These defects lead to a loss of membrane surface area, causing red blood cells to assume a spherical shape (spherocytes) rather than their normal biconcave disc shape. Spherocytes are less deformable and are prematurely trapped and destroyed in the spleen, resulting in chronic hemolytic anemia. The disease primarily affects the hematologic system, though secondary complications can involve the hepatobiliary system and skeletal system. Key clinical features include anemia of variable severity, jaundice (due to elevated bilirubin from red blood cell breakdown), splenomegaly (enlarged spleen), and an increased risk of pigmented gallstones, which may develop even in childhood or adolescence. The severity of HS varies widely, ranging from an asymptomatic carrier state to severe transfusion-dependent anemia. Aplastic crises, often triggered by parvovirus B19 infection, can cause a sudden and dangerous drop in hemoglobin levels. Neonatal jaundice requiring phototherapy or exchange transfusion may be the first presenting sign in affected infants. Diagnosis is typically established through a combination of clinical findings, family history, blood smear showing spherocytes, elevated mean corpuscular hemoglobin concentration (MCHC), reticulocytosis, and confirmatory tests such as the eosin-5-maleimide (EMA) binding test or osmotic fragility test. Treatment depends on disease severity. Folic acid supplementation is commonly recommended to support increased red blood cell production. For patients with moderate to severe disease, splenectomy (surgical removal of the spleen) remains the most effective treatment, substantially reducing hemolysis and anemia, though it does not correct the underlying red cell membrane defect. Partial splenectomy may be considered in young children to preserve some splenic immune function. Patients who undergo splenectomy require vaccinations against encapsulated organisms and long-term monitoring for infectious complications.

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