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Hereditary Elliptocytosis

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Description: Hereditary elliptocytosis is a genetic disorder characterized by abnormally shaped, elliptical red blood cells leading to varying degrees of hemolytic anemia.
Type: Hereditary elliptocytosis is a type of red blood cell disorder. The type of genetic transmission for hereditary elliptocytosis is autosomal dominant.
Signs And Symptoms: Hereditary elliptocytosis is a genetic disorder affecting red blood cells, leading to their elliptical shape rather than the typical biconcave disk shape. Signs and symptoms can include:

1. **Hemolytic Anemia**: Fatigue, weakness, and pallor due to the destruction of red blood cells.
2. **Jaundice**: Yellowing of the skin and eyes as a result of increased bilirubin from red blood cell breakdown.
3. **Splenomegaly**: Enlarged spleen, which can cause discomfort or pain in the upper left abdomen.
4. **Gallstones**: Due to increased bilirubin, which can form gallstones.
5. **Episodes of Hemolytic Crisis**: Exacerbations of hemolytic anemia, often triggered by infections.

The severity of symptoms can vary widely, from very mild, often unnoticed, to severe hemolytic anemia requiring medical intervention.
Prognosis: Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy.
Onset: Hereditary elliptocytosis typically has an onset from birth, though the severity of symptoms can vary widely among individuals. Some may be asymptomatic, while others might experience significant hemolytic anemia.
Prevalence: Hereditary elliptocytosis (HE) has a prevalence estimated at approximately 1 in 2,000 to 1 in 4,000 individuals in the general population. However, the prevalence can be higher in certain populations, such as those with African or Mediterranean ancestry.
Epidemiology: The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention. Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the United States, and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000, and in Malayan natives its incidence is 1500-2000 per 10,000. Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis.
Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively.
The following categorisation of the disorder demonstrates its heterogeneity:
Common hereditary elliptocytosis (in approximate order from least severe to most severe)
With asymptomatic carrier status
Intractability: Hereditary elliptocytosis is generally not considered intractable. While it is a chronic condition caused by inherited defects in the red blood cell membrane, many individuals with hereditary elliptocytosis are asymptomatic or have mild symptoms that do not require treatment. In more severe cases, management may include folic acid supplementation, blood transfusions, or splenectomy. The prognosis varies depending on the severity, but treatments are available to address symptoms and improve quality of life.
Disease Severity: Hereditary elliptocytosis is a genetic disorder affecting the red blood cells, causing them to be elliptical rather than the typical biconcave disc shape. The severity of hereditary elliptocytosis can vary widely among individuals. Some may remain asymptomatic with a normal lifespan, while others might experience hemolytic anemia, leading to symptoms like fatigue, jaundice, and splenomegaly. In severe cases, more frequent medical intervention and treatments such as splenectomy might be needed.
Healthcare Professionals: Disease Ontology ID - DOID:2373
Pathophysiology: Hereditary elliptocytosis (HE) is a genetic blood disorder characterized by the presence of elliptical or oval-shaped red blood cells. The pathophysiology of HE primarily involves mutations in genes encoding proteins of the red blood cell cytoskeleton, including spectrin, ankyrin, and protein 4.1. These mutations disrupt the stability and elasticity of the red blood cell membrane, making the cells more prone to deformation as they travel through the circulatory system. Consequently, these abnormally shaped red blood cells are often removed prematurely by the spleen, potentially leading to hemolytic anemia in severe cases.
Carrier Status: Hereditary elliptocytosis is an autosomal dominant disorder. This means that only one copy of the mutated gene inherited from an affected parent is sufficient to cause the disorder. Carriers typically show symptoms, but these can range from mild to severe. Very mild cases may be asymptomatic and go unnoticed.
Mechanism: Hereditary elliptocytosis (HE) is a genetic disorder that affects the red blood cells, causing them to be elliptical or oval-shaped rather than the typical biconcave disk shape. The primary mechanism behind this condition involves defects in the proteins that provide structural support to the red cell membrane.

**Mechanism:**
The elliptically shaped red blood cells are less flexible and more prone to breaking apart as they travel through the bloodstream, leading to hemolytic anemia. The main consequence is the disrupted shape and premature destruction of red blood cells, which hampers their ability to deliver oxygen efficiently throughout the body.

**Molecular Mechanisms:**
The molecular basis of hereditary elliptocytosis generally involves mutations in genes that encode for key cytoskeletal proteins, such as:

1. **Spectrin** (α and β chains):
- Spectrin is a primary component of the cytoskeleton, providing structural integrity.
- Mutations in the genes SPTA1 (α-spectrin) or SPTB (β-spectrin) can reduce the binding affinity of spectrin for other cytoskeletal components, leading to membrane instability.

2. **Protein 4.1R** (EPB41):
- This protein anchors the spectrin-actin complex to the plasma membrane.
- Mutations here can weaken the connection between the membrane and the cytoskeleton.

3. **Glycophorin C** (GYPC):
- Glycophorin C interacts with protein 4.1R and also contributes to membrane stability.
- Mutations in GYPC can disrupt these interactions, leading to elliptocytosis.

4. **Band 3 Protein (SLC4A1)**:
- Though less commonly involved, some mutations in Band 3 can also result in hereditary elliptocytosis.

In summary, hereditary elliptocytosis results from a compromised cytoskeletal network within red blood cells, primarily due to mutations in spectrin, protein 4.1R, and related components, which leads to their characteristic elliptical shape and decreased mechanical stability.
Treatment: The vast majority of those with hereditary elliptocytosis require no treatment whatsoever. They have a mildly increased risk of developing gallstones, which is treated surgically with a cholecystectomy if pain becomes problematic. This risk is relative to the severity of the disease.Folate helps to reduce the extent of haemolysis in those with significant haemolysis due to hereditary elliptocytosis.Because the spleen breaks down old and worn-out blood cells, those individuals with more severe forms of hereditary elliptocytosis can have splenomegaly. Symptoms of splenomegaly can include:
Vague, poorly localised abdominal pain
Fatigue and dyspnoea
Growth failure
Leg ulcers
Gallstones.Removal of the spleen (splenectomy) is effective in reducing the severity of these complications, but is associated with an increased risk of overwhelming bacterial septicaemia, and is only performed on those with significant complications. Because many neonates with severe elliptocytosis progress to have only a mild disease, and because this age group is particularly susceptible to pneumococcal infections, a splenectomy is only performed on those under 5 years old when it is absolutely necessary.
Compassionate Use Treatment: Hereditary elliptocytosis is primarily managed through supportive care and, in severe cases, more intensive treatments like splenectomy or blood transfusions. Currently, there aren't specific compassionate use treatments or widely recognized off-label/experimental treatments for this condition. Management mainly focuses on addressing associated symptoms, such as anemia, and preventing complications. Potential research areas might include gene therapies or advanced pharmacological approaches, but as of now, these are not established treatments for hereditary elliptocytosis.
Lifestyle Recommendations: For hereditary elliptocytosis, here are some lifestyle recommendations:

1. **Regular Check-ups**: Ensure regular consultations with a healthcare provider to monitor hemoglobin and red blood cell levels.

2. **Healthy Diet**: Maintain a balanced diet rich in iron, folic acid, and vitamins to support overall health and red blood cell production.

3. **Hydration**: Stay well-hydrated to help blood circulation and overall health.

4. **Avoiding Triggers**: Avoid situations that can trigger hemolysis such as extreme physical stress or infections.

5. **Exercise**: Engage in moderate, regular physical activity to maintain overall health, but avoid overly strenuous exertion that might exacerbate symptoms.

6. **Avoid Smoking and Alcohol**: These can exacerbate symptoms and negatively impact red blood cells and overall health.

7. **Protect Against Infections**: Stay up-to-date with vaccinations and practice good hygiene to prevent infections that could complicate the condition.

8. **Manage Stress**: Stress management techniques like yoga, meditation, or deep breathing exercises can promote overall wellness and potentially reduce symptom flare-ups.

9. **Medical Alert Identification**: Wear a medical alert bracelet or carry a card that explains hereditary elliptocytosis in case of emergencies.

10. **Avoid High-Altitude Locations**: High altitudes can lessen oxygen levels, increasing the risk of symptoms flaring up.

Always follow any additional advice given by your healthcare provider tailored to your specific condition.
Medication: There are no specific medications to treat hereditary elliptocytosis itself, as it is a genetic condition affecting the red blood cell membrane. Management typically focuses on addressing symptoms and complications, such as:

1. **Folic Acid Supplements**: To support red blood cell production.
2. **Blood Transfusions**: In cases of severe anemia.
3. **Splenectomy**: Surgical removal of the spleen in severe cases to reduce the destruction of red blood cells.

Consultation with a hematologist is recommended for personalized management plans.
Repurposable Drugs: There are no specific drugs that are currently repurposed for the treatment of hereditary elliptocytosis. The management of this condition primarily focuses on supportive care and addressing symptoms, such as treating anemia or managing complications.
Metabolites: Hereditary elliptocytosis, also known as ovalocytosis, is a genetic disorder affecting red blood cell shape. It is characterized by the presence of elliptically shaped erythrocytes in the blood. In the context of metabolites, there are no specific or unique metabolites identified exclusively for hereditary elliptocytosis. The diagnosis and monitoring of this condition typically involve hematological analysis rather than metabolite profiling.
Nutraceuticals: There are no established nutraceuticals specifically for hereditary elliptocytosis. This condition primarily affects the shape and flexibility of red blood cells due to genetic mutations. Management typically involves monitoring and supportive care, such as folic acid supplementation, especially when hemolysis is present. It is essential for individuals with hereditary elliptocytosis to work with their healthcare provider for appropriate diagnosis and treatment options.
Peptides: In hereditary elliptocytosis (HE), there is no direct or established connection to peptides or nanotechnology in standard treatments or diagnostics. HE is a genetic condition affecting red blood cell shape, typically caused by mutations in genes encoding proteins such as spectrin, ankyrin, or protein 4.1, which are crucial for the red blood cell cytoskeleton. Current management focuses on monitoring and treating symptoms rather than interventions involving peptides or nanotechnology.