What is Hereditary Elliptocytosis (Hereditary Ovalocytosis)?
Hereditary elliptocytosis, also known as hereditary ovalocytosis, is a condition someone is born with that affects their red blood cells (the cells that carry oxygen in our bodies). This condition causes the cells to have an elongated, oval, or ovoid shape instead of the typical round shape. This odd shape happened due to genetic changes in certain proteins (α-spectrin, β-spectrin, protein 4.1, band 3, and in rare cases, glycophorin C) that usually give the cells their normal stretchiness.
The spleen, an organ that usually filters and cleans our blood, sees these oddly shaped cells as abnormal and tries to get rid of them. This process can result in a type of anemia called hemolytic anemia. This condition was first noticed by a person named Dresbach in 1904, who confirmed that it is inherited from parents to their children.
There are various forms of this condition, each looking a bit different under a microscope and causing different amounts of cell destruction, or hemolysis. These include common hereditary elliptocytosis, hereditary pyropoikilocytosis (HPP), Southeast Asian ovalocytosis (SAO), and spherocytic elliptocytosis (SE).
Most people with hereditary elliptocytosis don’t show symptoms and, therefore, don’t need specific treatment. However, for those who do show symptoms, treatment may include blood transfusions (receiving donated blood) or splenectomy (removal of the spleen). These treatments aim to lessen the symptoms associated with the condition.
What Causes Hereditary Elliptocytosis (Hereditary Ovalocytosis)?
The flexibility of our red blood cells (RBCs) is mainly controlled by certain proteins located beneath the cell membrane. These include spectrin, ankyrin, protein 4.2, band 3 protein, and glycophorin C. Genetic abnormalities affecting these proteins can change their structure and function, resulting in unusual RBCs and compromised flexibility.
Hereditary elliptocytosis, a common blood disorder, typically happens because of genetic defects impacting proteins like α-spectrin, β-spectrin, protein 4.1, band 3, and sometimes glycophorin C. These genetic changes can be simple substitutions, insertions, deletions, or changes in how the gene instructions are read and carried out in the cell. The most common genes associated with these changes in hereditary elliptocytosis are SPTA1 for α-spectrin, SPTB for β-spectrin, and EPB41 for protein 4.1. Among these, the SPTA1 mutation is found in about 65% of cases, followed by SPTB (30%) and EPB41 (5%).
Hereditary elliptocytosis is usually inherited in an autosomal dominant pattern – which means you only need a mutation from one parent to get the disorder. However, a variant named HPP follows a unique pattern called autosomal recessive inheritance – which means you need a mutation from both parents to have the disorder. HPP is characterized by an α-spectrin mutation noted as α-LELY.
Risk Factors and Frequency for Hereditary Elliptocytosis (Hereditary Ovalocytosis)
Hereditary elliptocytosis is a condition that often goes unnoticed because many people with mild symptoms don’t get diagnosed. This makes it hard to know exactly how common it is, but it’s estimated that between 1 in 2000 and 1 in 4000 people worldwide have it. It’s most often found in people of African, Southeast Asian, or Mediterranean heritage. In West Africa, it’s much more common than elsewhere, with 1 to 2 percent of the population affected. This is about 10 times the rate seen in Europe and the US.
Out of all the people with hereditary elliptocytosis, less than 10% have a more severe form called HPP. Interestingly, the places where hereditary elliptocytosis is most common are also places where malaria is common. This has led some scientists to suggest that malaria might have helped spread the gene mutation that causes hereditary elliptocytosis.
- Specific versions of hereditary elliptocytosis, such as SAO, are especially common in Malaysia, Papua New Guinea, Indonesia, and the Philippines, where between 5% and 25% of people might have the condition.
- Another variant, SE, is more common in people of European descent.
Signs and Symptoms of Hereditary Elliptocytosis (Hereditary Ovalocytosis)
Hereditary elliptocytosis is a condition often discovered by accident during anemia testing. Even though many folks with this condition don’t have symptoms, some experience tiredness and difficulty exercising due to anemia. It’s important to know if other family members have anemia, as hereditary elliptocytosis could be confused with a condition like iron deficiency anemia. In rare cases, it may cause yellowing of a newborn’s skin and eyes, also called neonatal jaundice.
Long-term anemia associated with hereditary elliptocytosis can result in an enlarged spleen, leading to feeling full quickly, pain in the upper left side of the abdomen, and discomfort. Individuals with a severe form of the condition, known as HPP, may display a prominent forehead, while persistent break down of red blood cells can lead to painful leg ulcers. The signs and symptoms can vary depending on the specific type of hereditary elliptocytosis.
- The most common type of hereditary elliptocytosis is usually symptom-free. Newborns may have a brief period of red blood cell breakdown, which generally resolves within a year. In severe instances, newborns may have a high level of red blood cell destruction resulting in yellow tones to the skin and eyes, which could necessitate treatments such as blood transfusion and light therapy. The defining feature of this subtype is the presence of oval-shaped red blood cells on a blood smear test.
- HPP is considered the most severe subtype and primarily affects African-American newborns. These babies often have neonatal jaundice and continue to have an increased rate of red blood cell destruction throughout their lives. Complications such as an enlarged spleen and gallstones can develop, and treatments may involve blood transfusion and spleen removal.
- SAO, or stomatocytosis elliptocytosis, is typically seen in regions where malaria is common. People with this subtype may have mild or no red blood cell destruction and can have resistance against certain types of malaria. Blood tests may show specific shapes of red blood cells.
- SE is more common in people of Italian heritage and comes with mild to moderate red blood cell destruction. It can sometimes be difficult to differentiate from other types, and genetic analysis may be needed.
Physical check-ups may reveal pale skin in people with active red blood cell destruction. Other noticeable signs can include an enlarged spleen and upper right side abdominal pain, especially in those with gallstones due to red blood cell breakdown.
Testing for Hereditary Elliptocytosis (Hereditary Ovalocytosis)
If your doctor suspects you have a genetic condition called hereditary elliptocytosis, they’ll start by performing a thorough assessment, which will include a complete blood count (CBC). This is a standard blood test that checks for different types of cells in your blood. In people with hereditary elliptocytosis, this test can reveal a certain kind of anemia where red blood cells appear normal in size and color.
Another important test is a peripheral blood smear. This involves looking at a sample of your blood under a microscope. People with hereditary elliptocytosis typically show abnormal, elongated red blood cells, known as elliptocytes, in about 15% to 100% of red blood cells. Other abnormally shaped cells such as spherocytes (round cells), stomatocytes (mouth-shaped cells), poikilocytes (cells with irregular shapes), ovalocytes (oval-shaped cells), and macro-ovalocytes (large, oval-shaped cells) may also be seen.
Tests for a process called hemolysis (the breakdown of red blood cells) can also be done. These tests may reveal an increase in young red cells (reticulocytes), an enzyme called lactate dehydrogenase, a form of bilirubin (a waste product from the breakdown of red blood cells), and a decrease in a protein called haptoglobin. However, the number of elliptocytes in your blood does not always correlate with the severity of hemolysis.
For a more in-depth analysis, a test known as a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) can be performed. This test measures levels of certain proteins found in red blood cells. Additionally, morphological and genetic studies may be done by a procedure known as ektacytometry. This test looks at how red blood cell membranes react to light and pressure.
If the doctor suspects you have an enlarged spleen (splenomegaly), they may use an ultrasound. This is a simple, cost-effective imaging test that uses sound waves to create pictures of the spleen. If more detailed pictures are needed, they might also use a computed tomography (CT) scan or magnetic resonance imaging (MRI).
Treatment Options for Hereditary Elliptocytosis (Hereditary Ovalocytosis)
If a person doesn’t have any symptoms or red blood cell destruction (hemolysis), treatment or regular check-ups aren’t necessary. The most important thing is to inform the person about the nature of the illness. It’s also essential to document it in their health records to avoid unnecessary tests in the future.
When individuals experience intermittent hemolysis or anemia (low red blood cells), they may need blood transfusions. This is particularly the case if they have symptoms or if their hemoglobin (protein that carries oxygen in the blood) level falls below a certain limit, which is determined based on their age.
In severe cases, like extreme anemia that threatens a person’s life or the need for frequent blood transfusions, spleen removal (splenectomy) may be considered. However, before undergoing surgery, it’s essential that individuals get vaccinated against certain types of bacteria (pneumococcus, meningococcus, and Haemophilus influenza). This is necessary as the risk of infection by bacteria that have an outer layer (encapsulated organisms) increases after this kind of operation.
What else can Hereditary Elliptocytosis (Hereditary Ovalocytosis) be?
When diagnosing hereditary elliptocytosis, a condition where red blood cells are abnormally shaped, doctors look into a number of similar illnesses, which include:
- Hereditary spherocytosis
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Thalassemia: This, when paired with hereditary elliptocytosis, can show up as a patient not needing blood transfusions but having irregularly shaped and broken cells.
- Pyruvate kinase deficiency
- Hereditary stomatocytosis/xerocytosis
- Iron deficiency anemia
- Megaloblastic anemia
- Sickle cell anemia
- Myelofibrosis
- Myelodysplastic syndrome (a rare condition where abnormal ellipsoid cells can occur). The most common genetic defect connected with this syndrome is del20q.
What to expect with Hereditary Elliptocytosis (Hereditary Ovalocytosis)
Hereditary elliptocytosis, a condition where the blood cells are shaped like ellipses, usually doesn’t cause any symptoms in most patients. Still, a small percentage (5% to 20%) might experience an issue called uncompensated hemolysis, which leads to anemia or a lack of healthy red blood cells.
Those with severe hemolysis may need treatment with a procedure called splenectomy, which involves removing the spleen. Even in these cases, the prognosis is generally favorable, meaning they have a good chance of returning to health. This emphasizes that hereditary elliptocytosis is typically a mild condition.
Possible Complications When Diagnosed with Hereditary Elliptocytosis (Hereditary Ovalocytosis)
: Hereditary elliptocytosis comes with several complications:
- Megaloblastic anemia: This may be caused by a deficiency in folate and Vitamin B12 due to continuous destruction of red blood cells. This deficiency can result from poor nutrition, issues tied to high red blood cell production, or a mix of both. Taking supplements of Vitamin B12 or folate can help with this.
- Pigment gallstones: These can result in issues such as inflammation of the bile duct, inflammation of the gallbladder, and inflammation of the pancreas.
- Splenomegaly: Patients may experience an enlargement of the spleen, a condition that often accompanies many types of anemia related to the destruction of red blood cells.
- Renal tubular acidosis: This is connected with a specific subtype called SAO. With this subtype, families may see cases of a specific type of acid buildup in the blood tied to the kidneys.
- Leg ulcers: These are usually found around the inner ankle bones. It’s thought these occur in anemias related to the destruction of red blood cells due to blood pooling in these areas.
- Growth delay and abnormal bone structure: These issues can develop due to increased bone marrow expansion.
Preventing Hereditary Elliptocytosis (Hereditary Ovalocytosis)
It’s very important to teach patients and their families about how hereditary elliptocytosis, a genetic blood disorder, is passed down through families. This condition can be inherited in two ways – autosomal dominant or recessive. The term ‘autosomal’ refers to the fact that the gene in question is located on one of the numbered, or non-sex, chromosomes. ‘Dominant’ means that you only need to get the abnormal gene from one parent in order to inherit the disease. ‘Recessive’ means that you must get the abnormal gene from both parents to inherit the disease.
It’s recommended that family members get screened for hereditary elliptocytosis due to its genetic nature. For parents who have children severely affected by this condition, talking to a healthcare professional or counselor before having more children could provide valuable insights and guidance.
Patients who have had a surgical procedure to remove their spleen (splenectomy) need to receive vaccines and regular follow-up care to monitor for potential problems. Given the significant health issues related to hereditary elliptocytosis, it’s just as important to consider the risk for future generations as it is for the current one.
