Hereditary spherocytosis (HS) is an inherited condition that affects the red blood cells. The cells are damaged as they pass through the spleen and do not survive as long as normal blood cells. Typical early-stage symptoms include anemia, but patients will often develop other conditions as a result of hereditary spherocytosis.
There are four forms of hereditary spherocytosis, ranging from the mild form, the moderate form, the moderate/severe form, and the severe form. These forms are distinguished by their symptoms and severity levels. Estimates suggest that 20 to 30 percent of people will have mild HS, 60 to 70 percent will have moderate HS, 10 percent will have moderate/severe HS, and three to five percent will have severe HS.
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What Causes Hereditary Spherocytosis?
Mutations in the following genes have been implicated in hereditary spherocytosis:
Mutations in these genes are thought to be the cause of half of all cases of hereditary spherocytosis. These genes are responsible for stimulating the production of proteins that are found on red blood cell membranes. The proteins usually ensure that the membrane is flexible and the cell keeps its structure. However, mutations decrease the membrane’s flexibility, and make the red blood cells more prone to damage during their transit from bone marrow through the circulation.
Functional abnormalities and deficiencies involving the cytoskeletal protein spectrin have also been directly linked to hereditary spherocytosis.
Red Blood Cell Function and Structure
Red blood cells contain a protein called hemoglobin that enables them to carry oxygen around the body. Red blood cells also take carbon dioxide to the lungs to be exhaled and removed from the body. The typical lifespan of a red blood cell is 120 days, but in hereditary spherocytosis, red blood cells may only survive for 30 days.
Normal red blood cells are round with an indent in the center, and are often described as ‘donut-shaped’. All cells have a membrane that controls the movement of substances going in and out of the cell.
In hereditary spherocytosis, the surface membrane of red blood cells is unstable. This instability causes parts of the membrane to come away from the cell when it passes through the spleen and into the bloodstream. As a result, the shape of the cells is changed from their normal, donut-shaped discs to spheres, and consequently are called spherocytic red blood cells.
Spherocytic red blood cells are not as strong as normal blood cells and therefore do not survive as long as normal blood cells. They are taken out of the bloodstream and are destroyed in the spleen in a process called hemolysis. Bone marrow is not always able to keep up with making enough blood cells to replace those that have been destroyed by the spleen, which may lead to anemia.
Disorders Related to Hereditary Spherocytosis
Hereditary spherocytosis is not always noticeable at birth. However, non-specific symptoms may occur in young children that may indicate other conditions have developed stemming from HS.
For instance, anemia is very common in people living with mild hereditary spherocytosis. Jaundice, gallstones, and splenomegaly are also commonly experienced complications caused by hereditary spherocytosis.
Symptoms of anemia in young children include:
Not eating well
Older children and adults may become easily tired when exercising. Depending on the level of severity of HS, the severity of anemia will also vary.
Jaundice is a reversible condition that causes yellowing of the skin and the whites of the eyes and is seen in people with moderate HS. Levels of jaundice may vary over a person’s lifetime.
Jaundice is caused by a build up of bilirubin, a yellow waste material found in the blood when iron is removed from the blood. When bilirubin reaches the liver where waste is filtered from the blood, other chemicals attach to it creating a substance called conjugated bilirubin.
Conjugated bilirubin then enters the bile, also produced by the liver, and usually leaves the body. If there is an overproduction of bilirubin, it can leak into surrounding tissues and causes the skin and the whites of the eyes to become yellow in colour. Patients with spherocytosis can be jaundiced because hemolysis of red blood cells leads to increased bilirubin waste products.
Treatment of jaundice will depend on the underlying cause of the condition, as there are a number of illnesses that can cause jaundice. Jaundice brought on by anemia, which is often experience by those living with HS, can be treated with iron supplements.
Many people with HS will develop gallstones. These small stones form in the gallbladder, and cause pain in the abdomen and inflammation of the gallbladder. Blockage of bile can worsen jaundice.
Bile that is produced by the liver is passed to the gallbladder through bile ducts and helps to digest fats. Over time, bile becomes more concentrated and increases its efficacy in fat digestion.
Gallstones are usually made of cholesterol, and it is thought that chemical imbalances in the bile inside the gallbladder cause gallstones to develop.
Treatment is usually only sought if the gallstones are causing problems such as jaundice. In these cases, keyhole surgery can be carried out to remove the gallstones.
Splenomegaly is the name for an enlarged spleen. As the spleen’s main function is to filter blood, any damage caused to the spleen due to its enlarged size carries significant risk of substantial internal bleeding. In some cases, those with hereditary spherocytosis and anemia, the spleen is removed in a procedure called a splenectomy.
Symptoms of an enlarged spleen include:
Pain in the left side of the abdomen
Feeling full quickly after eating
People living with severe forms of hereditary spherocytosis may have skeletal abnormalities and not grow to their full height. Severe HS is characterized by severe anemia, sometimes requiring regular blood transfusions, and all of the symptoms seen in moderate HS. Sexual development may also be delayed in people with severe HS.
Diagnosis of Hereditary Spherocytosis
Hereditary spherocytosis can be diagnosed at any age. Diagnostic tests include:
Peripheral blood smear
Tests for iron levels in the blood
Osmotic fragility test
Flow cytometric analysis
Acidified glycerol lysis test.
Treatments for Hereditary Spherocytosis
There is currently no cure for hereditary spherocytosis. Treatments therefore focus on limiting the severity of the symptoms experienced by patients.
Folic acid is often prescribed to patients with HS as it helps the bone marrow to replace blood cells.
Splenectomies or partial splenectomies may be carried out in patients over the age of six. After a splenectomy, patients will be more susceptible to infections and will require regular doses of preventive medications and vaccinations.
The gallbladder may also be removed in some cases.
Risk Factors for Hereditary Spherocytosis
Children have a fifty percent chance of getting HS if one of their parents has the condition. Hereditary spherocytosis is more common in people of Northern European descent and in Japanese families, but is also common in North Africa and Brazil, and can occur in any ethnic group. It is estimated that approximately 25 percent of HS cases are due to spontaneous mutations.