Hereditary Elliptocytosis - Causes, Symptoms, and Treatment

What Is Hereditary Elliptocytosis?

Hereditary elliptocytosis is an inherited blood disorder affecting the structure of the red blood cell membrane, which is caused by a genetic mutation in genes like the alpha spectrum, beta spectrum, protein 4.1, and band 3; this mutation leads to a defective shape of the red blood cells membrane such as elongated, oval or elliptical shaped cells on the peripheral bloodstream.

Hereditary elliptocytosis was first introduced in 1904 by Dresbach and Hunter Firmly. Mostly, it is asymptomatic, and no treatment is required, but in some individuals, it may lead to severe conditions. Hereditary elliptocytosis is also called hereditary ovalocytotic.

What Are the Causes of Hereditary Elliptocytosis?

Hereditary elliptocytosis is caused by the inheritance of mutations in genes that affect the cytoskeletal structures of protein. Normal red blood cells originate from the hematopoietic stem cells in the bone marrow of the long bones in the body. They are normally biconcave in shape and circulate in the bloodstream for 120 days of a healthy life span with red pigmentation called hemoglobin. These red blood cells function as carriers of oxygen and important nutritional supplements to the organs of the body. The sequestration of red blood cells happens in the spleen after the completion of a healthy life span of 120 days.

The membrane of red blood cells is composed of bilayer lipids, which gives the strength and integrity to the cells to flow in the bloodstream without getting distracted. There are different proteins present in them that help to form the cytoskeleton structure of red blood cells, like spectrin, ankyrin, protein 4.1, protein 4.2, band 3, and glycophorin C.

The genetic mutations lead to variations in the protein like alpha spectrum, beta spectrum, protein 4.1, protein 3, and rarely glycophorin C; this results in structural deformity in the red blood cell membrane. The red blood cells lose their elastic nature, and while passing through microcirculation (like in small vessels), they are not able to regain their proper structure. This leads to the early death of red blood cells and also affects the severity of anemia caused by the early destruction of red blood cells.

What Are the Signs and Symptoms of Hereditary Elliptocytosis?

Hereditary elliptocytosis is caused by a genetic variation that leads to the inheritance of several conditions along with elliptocytosis.

1. Fatigue.

2. High-grade fever.

3. Chills.

4. Abdominal discomfort leading to pricking, throbbing abdominal pain.

5. Cholelithiasis (gallstones) are hard deposits in the gallbladder.

6. Abnormal red blood cells.

7. Congenital hemolytic anemia.

8. Elliptocytosis - Elliptical-shaped red blood cells seen over the peripheral smear.

9. Hemolytic Anemia.

10. Increased red blood cell osmotic fragility.

11. Pale or colorless skin caused by increased secretion of bilirubin leads to jaundice.

12. Postnatal growth retardation.

13. Prolonged neonatal jaundice.

14. Reticulocytosis - an increase in circulating reticulocytes (red blood cells that are still developing).

15. Splenomegaly (enlargement of the spleen).

16. Shortness of breath.

17. Tachycardia (a heart rate over 100 beats a minute).

18. Weight loss.

19. Frontal bossing (prominent forehead).

20. Leg ulcers.

What Are the Types of Hereditary Elliptocytosis?

Hereditary elliptocytosis is divided into four subtypes:

Common Elliptocytosis:

• It is the most common type of hereditary elliptocytosis.

• It is mostly asymptomatic.

• In newborns, it may lead to neonatal hemolytic anemia.

• Red blood cells are seen in an abnormal structure, like elliptical-shaped cells present in the peripheral blood smear.

Hereditary Pyropoikilocytosis:

• It is the most severe form of hereditary elliptocytosis commonly seen in African Americans.

• In newborns, neonatal jaundice, neonatal anemia with splenomegaly, and gallbladder stones are seen.

• In a peripheral blood smear, poikilocytes, spherocytosis, and some elliptical-shaped red blood cells are seen.

Southeast Asian Ovalocytosis:

• This subtype of hereditary elliptocytosis is also called stomatocytosis.

• It is associated with malaria-endemic regions.

• Mild or moderate symptoms of hemolytic anemia are seen. In a peripheral blood smear, cells like stomatocytosis, ovalocytosis, and macro-ovalocytosis are seen.

Spherocytic Hereditary Elliptocytosis:

• This form of hereditary elliptocytosis is rarely seen; usually, it is commonly seen in Italians.

• It has mild signs and symptoms of hemolytic anemia.

What Are the Investigations for Hereditary Elliptocytosis?

Hereditary elliptocytosis is mostly asymptomatic in nature, so certain blood and imaging investigations are performed for the conformational diagnosis of hereditary elliptocytosis.

1. Recording the patient's medical and family history, as hereditary elliptocytosis is a genetic disorder.

2. Physical examination helps to understand the signs and symptoms of the disorder.

3. Complete Blood Count (CBC) - This is a blood investigation test done to determine the count of red blood cells in the given sample of the patient's blood. Generally, in hereditary elliptocytosis, normocytic and normochromic anemia (normal number and normal color of red blood cells) are seen.

4. Peripheral Blood Smear - A small blood sample is collected, and a slide is prepared to examine the blood samples in the microscope. In hereditary elliptocytosis and stomatocytosis, ovalocytes, macro-ovalocytes, poikilocytes, spherocytes, and elliptical-shaped red blood cells are present and seen in the blood smear.

5. Reticulocytes Count Test - Reticulocytes are the cells present in the bloodstream; the level of reticulocytes gets elevated at the time of inflammation.

6. Lactate Dehydrogenase Test - Lactate dehydrogenase is an enzyme that gets secreted at the time of infection or inflammation. This test is done to determine the level of the enzyme.

7. Bilirubin Level - A bilirubin test is done to determine the gallbladder stone and jaundice.

8. Haptoglobin Test - Haptoglobin is an enzyme that gets decreased in hereditary elliptocytosis.

9. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis is done to determine protein 4.1 and spectrin quantitation.

10. Ultrasound sonography or computed tomography is advised for splenomegaly.

What Are the Treatment Modalities for Hereditary Elliptocytosis?

• Hereditary elliptocytosis is a genetic blood disorder that can be asymptomatic and does not need any treatment.

• In the severe causes of elliptocytosis, blood transfusion is advisable, or in patients with hemolytic anemia.

• Splenectomy is done for life-threatening conditions such as severe splenomegaly and the requirement of continuous blood transfusion.

• It can be treated along with supportive treatment for other underlying diseases.

Conclusion

Hereditary elliptocytosis is a rare genetic red blood cell disorder leading to hemolytic anemia caused by the structural disability of the red blood cells. The characteristic feature of hereditary elliptocytosis is the elliptical-shaped red blood cells. Mostly it is asymptomatic and does not require any treatment. Therefore, living with elliptocytosis is manageable with blood transfusion and supportive treatment.