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◉ What is Hereditary Spherocytosis?
Hereditary spherocytosis is a type of a genetic disorder that affects red blood cells, causing them to take on a spherical shape instead of their normal biconcave disc shape.
These abnormally shaped cells are less efficient, less flexible, more fragile and prone to breakage, which causes the spleen to break down faster than it needs to. This results in a medical condition known as hemolytic anemia.
Hereditary spherocytosis shortens red blood cell lifespan to around 30 days (compared to the usual 120 days), causing anemia, jaundice, elevated bilirubin, and an increased risk of gallstones.
Clinical severity is variable, with some individuals remaining asymptomatic, while others endure severe hemolytic anemia, necessitating red blood cell transfusion..
◉ Causes
Hereditary spherocytosis (HS) occurs due to a variety of mutations causing defects in red blood cell membrane proteins.
As a result of genetic mutations in red blood cell membrane proteins, the cytoskeleton loses its stability. The loss of erythrocyte surface area leads to the production of spherical RBCs (spherocytes).
This disorder is transmitted as an autosomal dominant trait. Mutations in ANK1 are the most common cause of hereditary spherocytosis, followed by mutations in SPTB and SLC4A1.
Recessive inheritance represents 10% of all hereditary spherocytosis cases. It occurs due to mutations in SPTA1 and EPB42.
◉ Symptoms and Signs
Most patients with hereditary spherocytosis have a positive family history. A doctor should suspect HS in any child presenting with splenomegaly, anemia, and hyperbilirubinemia.
◉ 1. Anemia
Spherocytosis causes spherocytes to break down at a faster rate than healthy RBCs. This can lead to anemic manifestations:
- Fatigue
- Shortness of breath
- Dizziness
- Increased heart rate
- Pale skin
- Headache
- Palpitations.
◉ 2. Jaundice
Jaundice is the result of excessive RBCs breakdown as too much bilirubin is released into the blood.
Excess bilirubin can cause jaundice which is the yellowing of skin and eyes. This is considered one of the most important signs of hemolytic anemia.
◉ 3. Gallstones
Gallstones are a normal result of excess bilirubin. They develop when too much bilirubin gets into the gallbladder.
Symptoms may not appear unless blockage has happened by gallstones. Symptoms of this condition may include:
- Sudden pain in the upper right abdomen
- Sudden pain in the right shoulder
- Nausea and vomiting
- Decreased appetite
- Fever
- Jaundice
◉ 4. Enlarged spleen (splenomegaly)
Blood cells traverse the spleen by navigating through narrow passageways before re-entering the bloodstream. Inside the spleen, red blood cells are filtered, with aging or abnormal ones breaking down.
While normally disc-shaped red blood cells move seamlessly within the spleen, spherocytes face difficulties. Spherical spherocytes, however, struggle to pass through the spleen's constricted passages, leading to their entrapment within the organ.
As the spleen endeavors to accommodate this substantial quantity of abnormal red blood cells, it consequently enlarges, resulting in the development of splenomegaly.
◉ 5. Symptoms in children
Jaundice is the most common symptom of HS in newborns, especially in the first week of life. Symptoms in children may include:
- Yellowing of eyes and skin
- Irritability
- Difficulty feeding
- Excess sleep
- Produces less than 6 wet diapers per day
The onset of puberty may be delayed in children diagnosed with hereditary spherocytosis.
◉ Diagnosis
The diagnosis of hereditary spherocytosis involves several steps including:
◉ 1. Medical history
Healthcare providers may require some information about the patient's medical background including:
- Family history
- Prior diseases
- Medications
This disease is strongly suspected in the presence of family history, simultaneously with hemolytic anemia symptoms.
◉ 2. Discussion
The doctor may ask you some questions about your symptoms, regarding the onset of symptoms, severity of them, and the presence of jaundice or other manifestations.
◉ 3. Physical examination
Physical examination is done to detect physical symptoms of hereditary spherocytosis, such as an enlarged spleen.
◉ 4. Laboratory tests
Laboratory tests are the perfect method for the diagnosis of HS. The tests may include:
- Complete blood count (CBC): This test provides your doctor with information about RBCs count, size, and hemoglobin content. It also reveals the state of white blood cells and platelets.
- Peripheral blood smear: This test helps healthcare providers check blood cells' size and shape.
- Reticulocyte count: Reticulocytes are immature RBCs. This test reveals bone marrow's ability to produce a sufficient amount of healthy red blood cells.
- Coombs test: This test checks for autoimmune hemolytic anemia, so it's considered to be negative in case of hereditary spherocytosis.
- Bilirubin level: Usually it's high. This test checks the bilirubin level in the blood. It's expected to increase as a result of RBCs hemolysis.
- Red cell osmotic fragility: This test checks red blood cells' capability to break down.
- Plasma membrane electrophoresis: A technique dependent on the use of a gel or fluid on an electric field to identify DNA, RNA, or proteins. This test helps healthcare providers to identify which membrane proteins are mutated.
Diagnosis is considered positive in case of:
- Coombs negative result with increased mean corpuscular hemoglobin concentration (MCHC) (increased concentration of hemoglobin in spherocyte red blood cells).
- Positive history for hereditary spherocytosis and spherocytes on microscopy.
- Positive test in red cell osmotic fragility test.
◉ Treatment
There is no cure for hereditary spherocytosis. Treatment focuses on improving the quality of life and preventing complications of the disease.
Treatment varies according to the symptoms:
- Splenectomy: It's the definitive treatment of HS. It usually eliminates hemolysis and associated manifestations except in the autosomal recessive variant of HS.
- Cholecystectomy: It's indicated in the presence of gallstones.
- Iron chelation therapy: Frequent blood transfusion may lead to hemochromatosis, so iron chelation therapy eliminates excess iron from the body.
- Neonates with severe hyperbilirubinemia should be treated with phototherapy and/or exchange transfusion.
◉ Conclusion
Hereditary spherocytosis is one of the most serious diseases. Jaundice is a common manifestation of HS. The patient is highly suspected of HS in case of jaundice or anemic symptoms with a positive family history of HS.