Brief overview
- Description: Globular cell anemia is a congenital disorder that usually causes anemia in infancy or early childhood. Causes: Gene mutations that cause defects in red blood cells.
- Symptoms: Pallor, fatigue, anemia, jaundice, splenomegaly, gallstones.
- Diagnosis: Physical examination, positive family history, blood test, ultrasound
- When to see a doctor: Sudden onset of pallor, increasing fatigue associated with febrile infections, headache or abdominal pain
- Treatment: Blood transfusions, removal of the spleen, removal of the gallbladder
- Prevention: Since it is a congenital gene mutation, no prevention is possible.
- Prognosis: With early detection and treatment of spherocytic cell anemia, the prognosis is very good; affected individuals have a normal life expectancy.
What is spherocytosis?
Globular cell anemia (hereditary spherocytosis) is a genetic, congenital disorder that causes a change in red blood cells. It belongs to the group of hemolytic anemias. This refers to anemia caused by increased or premature breakdown of red blood cells (hemolysis). Globular cell anemia is not contagious and is not acquired during life.
In spherocytosis, the erythrocytes are deformed due to a gene mutation. Instead of the normal disc shape, they become spherical (spheroid), which gives the disease its name (hereditary spherocytosis). Because the spherical erythrocytes are smaller than healthy ones, doctors also refer to them as microspherocytes.
The spleen is part of the immune system and is responsible, among other things, for breaking down old and defective erythrocytes. In spherocytic anemia, the spleen recognizes the altered red blood cells as foreign, filters them prematurely from the bloodstream and degrades them. As a result of the massive breakdown of the altered blood cells, affected individuals eventually develop anemia. Depending on how the lack of red blood cells affects the body, a distinction is made between four degrees of severity of spherocytosis: mild, moderate, severe and very severe.
Frequency
Globular cell anemia is by far the most common congenital hemolytic anemia, but is considered a rare disease overall: It affects about one in 5,000 people in Central Europe.
Globular cell anemia and childbearing
In the case of autosomal-dominant inherited spherocytosis, the probability of passing the disease on to the child is 50 percent, in the case of autosomal-recessive it is 25 percent. However, it is also possible to bring a completely healthy child into the world.
How does spherocytosis develop?
The cause of spherocytosis is congenital gene mutations. They cause the “coating” of the red blood cells (erythrocyte membrane) to become unstable. The “envelope” becomes more permeable because certain components of the membrane are missing or no longer functional. Water and salts (especially sodium) can flow in more easily and inflate the red blood cells. This causes them to change: they lose their natural disc shape and become spherical.
The genes for the membrane proteins “ankyrin”, “band 3 protein” and “spectrin” are most frequently affected; changes in the genes of “protein 4.2” and “Rh complex” occur less frequently.
How is spherocytosis inherited?
In 75 percent of all affected individuals, the disease is inherited in an autosomal dominant manner. This means that the disease is passed on to the child even if only one parent carries the gene mutation. The altered genetic material becomes dominant – the disease breaks out.
In addition, there are so-called “carriers”: affected individuals carry altered genes without contracting the disease themselves. Nevertheless, they can pass the disease on to their offspring.
Symptoms
The symptoms of spherocytosis depend on the severity of the disease and its course. The symptoms vary from patient to patient. Some affected individuals are completely symptom-free and are diagnosed only by chance, while others have severe symptoms as early as childhood.
Typical symptoms of spherocytosis
Anemia: When the spleen breaks down too many blood cells, they are missing from the blood and anemia results. Since erythrocytes are responsible for oxygen transport, the body is no longer supplied with sufficient oxygen. Affected individuals therefore develop non-specific symptoms such as pallor, fatigue, loss of performance and headaches.
Jaundice (icterus): Due to the excessive breakdown of red blood cells, increased amounts of breakdown products such as bilirubin are produced. Bilirubin causes typical jaundice symptoms such as yellowing of the skin and eyes. It forms when the red blood pigment hemoglobin is broken down along with the erythrocytes. This is normally responsible for the transport of oxygen and carbon dioxide.
Gallstones (cholelithiasis): The breakdown products of red blood cells can clump together in the gallbladder and form gallstones, which in turn irritate and/or obstruct the gallbladder or bile duct. Severe pain in the upper abdomen is then typical. If an inflammation also develops, fever and chills are also present.
Possible complications of spherocytosis
Aplastic crisis: In an aplastic crisis, the bone marrow temporarily stops producing red blood cells. However, as the spleen continues to break down the defective blood cells, there is a sudden sharp decrease in red blood cells. The body is no longer supplied with sufficient oxygen. Affected persons then almost always need a blood transfusion.
The aplastic crisis is often triggered in patients with spherocytic cell anemia by an infection with ringworm (parvovirus B19). Affected individuals usually become infected in childhood. After surviving the infection, they are usually immune for life.
Ringworm is easily overlooked in children with spherical cell anemia because they lack the typical ringworm symptoms such as the butterfly-shaped rash on the cheeks and the garland-shaped rash on the arms, legs and trunk!
Call 911 immediately if you suspect a hemolytic crisis!
Diagnosis
The first signs of spherocytic cell anemia often become apparent in infancy or early childhood. In mild cases, it is possible that the suspicion of the disease arises only by chance during a blood test.
The diagnosis is usually made by a specialist in blood disorders in children and adolescents (pediatric hematologist). The physician performs several tests for this purpose, since there is no one test that can be used to unequivocally diagnose spherocytosis.
The diagnosis includes:
Medical history (anamnesis): During the initial consultation, the physician inquires about the course of the disease and current symptoms. If there are already cases of spherocytosis in the family (positive family history), this is a first indication of the disease.
Physical examination: The doctor then examines the patient, paying particular attention to typical symptoms of spherocytosis, such as pallor, abdominal pain and jaundice.
Globular cells also occur in people who do not have globular cell anemia. Sometimes they are temporarily found in the blood in burns, certain infections or after a snake bite.
Ultrasound examination: The doctor can detect spleen enlargement or gallstones beyond doubt by means of ultrasound examination.
When to see a doctor?
Globular cell anemia is usually diagnosed in infancy or toddlerhood. A visit to the doctor is necessary when affected individuals develop symptoms such as sudden pallor, increasing fatigue, febrile infections, headaches or abdominal pain.
Treatment
Since the cause of spherocytosis is a gene mutation, there is no treatment that cures the disease causally. Thus, therapy is primarily aimed at alleviating symptoms and preventing complications. In most cases, however, spherocythemia can be treated well, so that those affected have a normal life expectancy.
Removal of the spleen (splenectomy): Removal of the spleen causes the altered blood cells to break down more slowly and consequently survive longer. This prevents anemia from occurring.
Since the spleen is important for defense against pathogens, it is not completely removed, a small part is retained. This allows the remaining spleen to continue to produce defense cells (antibodies) against certain pathogens as part of the immune system.
In severe and very severe courses, the spleen is removed before school entry age. In moderately severe cases, between the ages of seven and ten.
Removal of the gallbladder (cholecystectomy): In patients who develop gallstones during the course of the disease, it may be necessary to remove the gallbladder.
IMPORTANT: Not all of the above forms of treatment are necessary in every patient. Which therapy is used always depends on the individual course of the disease!
After splenectomy
Since the spleen is an important part of the immune system, the risk of infections increases after its removal. The same applies to blood clots (thromboses), stroke and heart attack.
To prevent the consequences of spleen removal, doctors give the following recommendations:
Vaccinations: Children with spherocytosis who have had their spleens removed are vaccinated in the same way as healthy children according to current recommendations. It is particularly important that those affected are protected against pathogens such as pneumococcus (pneumonia), meningococcus (meningitis) and Haemophilus influenzae type b (meningitis, epiglottitis).
Regular check-ups with the doctor: Patients who have had their spleen removed are advised to have regular check-ups.
Healthy and balanced diet: In addition, patients should ensure adequate folic acid and vitamin B12 intake.
Prognosis
If spherocytosis is detected and treated early, the prognosis is very good, and affected individuals usually have a normal life expectancy.
Prevention
Because spherocytosis is genetic, there are no measures to prevent the disease. Parents who are carriers of the genetic mutations or who themselves suffer from spherocytosis can seek human genetic advice. After a blood test of the parents, the human geneticist estimates the risk of passing the disease on to the child.