What Is Spherocytosis?

Spherocytosis is a condition that causes a person’s red blood cells to be shaped like spheres (round balls) instead of their normal disk shape. It can cause symptoms of anemia (lack of healthy red blood cells) and an enlarged spleen (an organ that filters and stores blood).

This condition is usually inherited. It is caused by various genetic changes that affect proteins in the outer membrane of the red blood cells.

Types of Spherocytosis

There are four types of spherocytosis, and they are differentiated by the severity of the condition. 

The types of spherocytosis are:

• Mild: This type rarely causes symptoms, or symptoms may occur when there is a triggering factor. 
• Moderate: This is the most common type, and it causes moderate symptoms. This type generally requires ongoing monitoring and treatment as needed. 
• Moderate/severe: This type can cause frequent symptoms and may require splenectomy (surgical removal of the spleen). 
• Severe: This type may require frequent blood transfusions and can be life-threatening. 

The types have also been characterized as trait, mild, moderate, and severe. 

The specific type of spherocytosis a person has is related to the specific genetic variation and which red blood cell protein is affected. 

What Are the Symptoms of Spherocytosis? 

Spherocytosis can cause symptoms that begin during childhood and continue throughout a person’s life. The severity of symptoms can range from very serious to mild, and the symptoms and effects can occur frequently or rarely. 

Sometimes symptoms are triggered by stresses to the body, such as an infection. 

Common symptoms and effects of spherocytosis:

• Anemia: Causes fatigue and pale skin
• Hemolysis (breakdown of the red blood cells): Causes jaundice (yellow discoloration or the skin and whites of the eyes)
• Splenomegaly (an enlarged spleen): Causes the abdomen to appear large and can cause shortness of breath from pressure on the lungs
• Gallstones (hard stones forming in the gallbladder): Can cause abdominal pain and a decreased appetite

These symptoms can occur intermittently, and they can improve with treatment.

Complications

Spherocytosis can make a person susceptible to severe anemia or infections. A severely enlarged spleen could rupture, which is dangerous.

What Causes Spherocytosis?  

Spherocytosis occurs when the red blood cell membrane lacks certain proteins that provide flexibility to the membrane. The defective proteins associated with this condition include a-spectrin, b-spectrin, ankyrin, band 3, and band 4.2.

This structural membrane defect causes the red blood cells to have a spherical shape, and it can cause hemolysis (breaking down) of the red blood cells.

Red blood cell hemolysis leads to anemia. Accumulation of red blood cell components in the spleen causes splenomegaly. Accumulation of bilirubin (from the breakdown of red blood cells) causes gallstones. 

Inheritance

Spherocytosis is usually hereditary, passed on from parents to children. Usually, the inheritance pattern is autosomal dominant. This means it is passed on chromosomes other than X and Y and that anyone who has the gene will develop the illness.

Sometimes it is inherited in an autosomal recessive pattern, which means that a person needs to have two copies of the disease-causing gene (one from each genetic parent) to develop the condition. Parents who are carriers might not experience any effects, and it rarely can develop without being inherited. 

Genetics

The most common defect that can cause spherocytosis is the ANK1 gene, which codes for ankyrin protein. The condition can also be caused by a defect on the EPB42 (codes for protein 4.2), SLC4A1 (codes for band 3), SPTA1 (codes for a-spectrin), and SPTB (codes for b-spectrin) genes.

Each of these genes is associated with a different membrane protein defect. It typically only takes one of the gene defects to cause the condition. People with nonhereditary forms of spherocytosis also develop a genetic defect, but it is not inherited.

How Is Spherocytosis Diagnosed? 

You may have signs of spherocytosis that your doctor can detect with a physical examination, such as pale skin, jaundice, an enlarged abdomen, or a palpable (can be felt by touch) spleen. With spherocytosis, these signs are not always present.

Spherocytosis is diagnosed with blood tests that evaluate characteristics of the red blood cells and with genetic testing. 

Common blood tests that may raise concerns about spherocytosis include:

• Complete blood count (CBC): The hemoglobin level (the protein that carries oxygen in red blood cells) and reticulocyte count (a count of young red blood cells) are associated with the severity of spherocytosis.
• Peripheral blood smear: This microscopic examination will show a spherical shape, small size, and deep stain of the red blood cells.
• Bilirubin test: Bilirubin is a product of red blood cell breakdown. It can be measured in the blood.

Specific tests may be ordered if there is a concern about spherocytosis.

These include:

• Eosin-5-maleimide binding (EMA) test: Measures the binding of EMA to the red blood cell plasma membrane. The binding is low in spherocytosis
• Acidified glycerol lysis time (AGLT): Measures breakdown of the red blood cells, which is increased in spherocytosis

Treatments for Spherocytosis 

This condition can be managed with medical care, and sometimes surgical intervention is needed. Spherocytosis is not curable, but medical attention can help improve the outcome and quality of life and prevent complications. 

Treatments include:

• Folate: Sometimes, folate supplementation can help improve red blood cell formation.
• Iron: Supplementation with this mineral can help improve red blood cell count, especially if there has been substantial hemolysis.
• Blood transfusion: This can be done when red blood cell levels are very low.
• Splenectomy: Surgical removal of the spleen can include total or partial splenectomy if splenomegaly is severe. Splenectomy can reduce hemolysis. Total splenectomy can increase susceptibility to infections.
• Immunizations: Infections can trigger hemolysis, and people who have spherocytosis may also be at an increased risk of infections, so vaccination for preventable infections is recommended.
• Treatment for gallstones: Surgery or other procedures may be needed if gallstones cause severe pain.

Summary

Spherocytosis is a red blood cell disorder that is usually inherited. It is a lifelong disease that causes red blood cells to be susceptible to excessive hemolysis (breakdown) due to a defect in the membranes of the red blood cells. The condition varies in severity from mild to severe, and treatment can help alleviate symptoms and prevent complications.

A Word From Verywell 

Spherocytosis is usually hereditary. If you're diagnosed with the condition, you might already have other family members who also have it. You may consider getting genetic testing or other diagnostic tests for yourself or your children if you have family members diagnosed with spherocytosis.

While the condition requires ongoing medical surveillance and might require repeated treatment, it can usually be managed with medical attention.