Hereditary spherocytosis

Hereditary spherocytosis is a type of hemolytic anemia caused by a defect in the red blood cells (RBCs) membrane that become them fragile and vulnerable to the destruction in the spleen.

The normal shape of human RBCs, also called erythrocytes, is biconcave. The biconcave shape allows RBCs to bend and to flow through small blood vessels. In contrast, in hereditary spherocytosis, RBCs have a spherical or round shape. They are less deformable and break down more quickly than normal RBCs. Abnormal spherocytes become trapped and are usually destroyed in the spleen.

Hereditary spherocytosis is a genetic disorder caused by mutations in the genes that encoded the membrane proteins of RBCs.

The genes affected may be the following ones:

• Gene SPTA1 in chromosome 1 (1q21)
• Gene ANK1 in chromosome 8 (8p11.21)
• Gene SPTB in chromosome 14 (14q23.3)
• Gene EPB42 in chromosome 15 (15q15.2)
• Gene SLC4A1 in chromosome 17 (17q21.31)

It is a hereditary disease passed down from parents to children. In some rare cases, spherocytosis is due to spontaneous mutation of the genes.

In 75% of the cases, it follows an autosomal dominant inheritance pattern, in 10% it is an autosomal recessive disorder and in 15% it is caused by a spontaneous mutation.

Hereditary spherocytosis incidence is about 1 in 5,000 people.

The most common symptoms of the disorder are:

• Anemia: A low RBC count in the blood due to the destruction of RBCs in the spleen. Fatigue is considered the main symptom of anemia.
• Jaundice: The skin and whites of the eyes will turn yellow due to the increase of bilirubin. Bilirubin is produced when RBCs are destroyed.
• Choluria: Dark or brown urine due to the excretion of bilirubin in the urine.
• Splenomegaly: Enlargement of the spleen due to RBC retention and premature removal by the spleen.

In some cases, stress or vigorous exercise may narrow capillaries (tiny blood vessels) and lead to a massive destruction of RBCs over a short time called hemolytic crisis.

In a blood test, there will be a high percentage of defective RBCs (spherocytes).

Unconjugated or indirect bilirubin will have values between 1 to 4 mg/dl (mild unconjugated hyperbilirubinemia).

There is no specific treatment. In some patients who have severe anemia, splenectomy (surgical removal of the spleen) improves the anemia by removing the major site of red cell destruction. Splenectomy in children from 5 to 8 years of age or older may be needed for serious cases.

The spleen breaks down fragile RBCs and remove them from the bloodstream. When the spleen is removed, hemolysis (rupture of RBCs) will occur in other organs such as the liver but not in a massive and sudden way.

Splenectomy also prevents hemolytic crises.

Without a spleen, a person has an increased risk for some serious infections, particularly in children. For this reason, vaccinations and use of preventive antibiotics decrease this risk of infections.

Possible complications include:

• Infections after splenectomy
• Hemolytic crisis
• Aplastic crisis triggered by B19 parvovirus infection
• Cholelithiasis (bilirubin gallstones)