Hereditary spherocytosis

One of the most common red cell membrane disorders with a frequency of 1 in 2000-5000 depending on the population.

Clinically ranges from mild to severe anemia that is transfusion dependent.

Mutations in red blood cell membrane proteins, ankyrin, band 3, protein 4.2 and beta-spectrin account for more than 90% of cases.

Hereditary spherocytosis is a genetically-transmitted autosomal dominant form of disease, with a 50% chance of passing the mutation to one’s offspring.

Most commonly found in Northern European and Japanese families.

Estimatedv 25% of cases are due to spontaneous mutations.

Caused by molecular defects in the genes that code for spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other erythrocyte membrane proteins.

The above proteins are necessary to maintain the normal shape of an erythrocyte, which is a biconcave disk.

The integrating protein that is most commonly defective is ankyrin which is responsible for incorporation and binding of spectrin.

The above defects lead to an impaired RBC cytoskeleton.

It is an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped, and therefore prone to hemolysis.

Results in observational symptoms of fatigue, pallor, and jaundice.

Results in varying degrees of anemia and hyperbilirubinemia.

Acute severe cases may be associated with acute kernicterus through hyperbilirubinemia, particularly in newborns.

Most cases can be detected soon after birth, but occasionally, the disease will not be diagnosed until the child is about 4 or 5 years of age.

Chronic symptoms include anemia,and splenomegaly.

As a result of breakdown of red blood cells, unconjugated or indirect hyperbilirubinemia is associated with bilirubin accumulation in the gallbladder, which can cause pigmented gallstones to develop.

An infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis.

Spherocytosis patients may suffer from iron overload, and this is especially true for those who are heterozygous for a hemochromatosis gene.

Measuring iron stores is part of the diagnostic approach to hereditary spherocytosis.

The peripheral smear shows abnormally small red blood cells lacking the central pallor.

An osmotic fragility test can aid in the diagnosis, as spherocytes will rupture in mildly hypotonic solutions – this is due to increased permeability of the spherocyte membrane to salt and water.

The spleen normally targets abnormally shaped red cells and destroys spherocytes.

As RBCs pass from the cords of Billroth into the sinusoids they must be flexible to pass through, and cells of hereditary spherocytosis may fail to pass through and get phagocytosed, causing extravascular hemolysis.

Hemolytic crisis may be precipitated by infection.

Aplastic crisis usually due to maturation arrest, and often associated with megaloblastic changes may be precipitated by infection, such as influenza, and particularly with parvovirus.

May be associated with floater deficiency caused by increased requirement, pigmented gallstones, leg ulcers, and abnormally low hemoglobin A1C levels.

Symptoms of anemia and hyperbilirubinemia dictate need for blood transfusions.

Dietary supplementation with frolic acid is required.

With severe hemolysis splenectomy may be required in the management

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