Hereditary Spherocytosis

What is hereditary spherocytosis?

Hereditary spherocytosis is an inherited blood disorder that causes hemolytic anemia. This anemia happens when your red blood cells break down faster than normal. In hereditary spherocytosis, your red blood cells lose their characteristic disk-like shape, becoming round or spherical cells (spherocytes) that are removed from circulation faster than normal red blood cells.

Who is affected by hereditary spherocytosis?

Hereditary spherocytosis typically affects people who have Northern Europe or North American ancestry. (Northern Europe is the northern part or region of the European continent.) Data vary on how many people have hereditary spherocytosis. Healthcare providers estimate that 1 person in 2,000 to 5,000 people worldwide may have hereditary spherocytosis. (The 2021 global population was 7.9 billion.)

Healthcare providers typically diagnose hereditary spherocytosis in infants and young children. Some people, however, don’t have signs or symptoms until ages 30 to 40. Many times, children who have the condition start having symptoms between ages 3 and 8. In some cases, healthcare providers diagnose newborns after doing blood tests for hereditary spherocytosis. They do the blood tests for infants who had severe anemia symptoms about a week after they were born.

How does hereditary spherocytosis affect my body?

In addition to developing hemolytic anemia, most people who have hereditary spherocytosis may have the following conditions:

• Enlarged spleen (splenomegaly): People develop enlarged spleens in hereditary spherocytosis when their spleens fill up with spherocytes. Blood cells flow through your spleen, navigating several narrow passages before moving on to your bloodstream. Your spleen serves as blood cell quality control. It filters red blood cells, identifying and breaking down aging, abnormal or damaged blood cells. Normal disk-shaped red blood cells flow through your spleen. Round spherocytes can’t get out, so they’re trapped in your spleen, which expands to make room for the unusually large number of blood cells.
• Jaundice: This condition affects your skin, the whites of your eyes (sclera) and your mucous membranes, causing them to turn yellow. This happens when you have a high level of bilirubin caused by a breakdown of your red blood cells.
• Gallstones: High bilirubin levels may cause gallstones.

Hemolytic anemia symptoms

Hemolytic anemia symptoms include jaundice and enlarged spleens. Other symptoms are:

• Shortness of breath (dyspnea): This happens when you don’t have enough red blood cells carrying oxygen throughout your body.
• Fatigue: Fatigue is a sensation of being so tired that it affects your daily life and your ability to do your daily activities.
• Fast heartbeat (tachycardia): This condition means your heart is beating faster than it should. When your heart beats too fast, it doesn’t have enough time between beats to fill up with blood, and your heart can’t supply your body with the oxygen it needs.
• Low blood pressure (hypotension): Low blood pressure can be a symptom or a condition. It happens when your blood pressure is much lower than expected.

Does everyone who has hereditary spherocytosis develop one or all of these conditions?

No. Most healthcare providers categorize hereditary spherocytosis as being mild, moderate or severe based on condition signs and symptoms. (Some healthcare providers have a fourth category: moderate/severe.) Here’s more information:

• Mild: This category includes about 20% to 30% of people who have hereditary spherocytosis. People in this category have hemolytic anemia. They typically don’t have other symptoms until they’re in their 30s or 40s.
• Moderate: This category includes babies and children who have hereditary spherocytosis and represents 60% to 75% of all people who have the condition. Babies and children may have mild to moderate hemolytic anemia and jaundice.
• Severe: This category represents 5% of all people who have hereditary spherocytosis. It includes newborns who develop severe anemia symptoms when they’re about a week old.

What causes hereditary spherocytosis?

As the name implies, people inherit this condition from their biological parents. Everyone receives copies of their biological parents’ genes. Inherited disorders happen when genes passed on from parent to child mutate or change. In hereditary spherocytosis, parents may pass on mutations in five different genes. These genes provide instructions to proteins that make up part of red blood cells’ infrastructure. (This genetic mutation also determines whether someone has a severe or mild form of hereditary spherocytosis.)

About 75% of people who have hereditary spherocytosis inherit the condition in an autosomal dominant manner. That means it only takes one copy of the responsible gene to cause some form of hereditary spherocytosis. Children born to a parent who has the mutated gene have a 50% chance of inheriting the mutated gene.

Other people inherit the condition because they received one copy of mutated genes from each parent. This is autosomal recessive manner. In this case, parents are carriers but usually don’t have hereditary spherocytosis signs or symptoms.

When people who are carriers have children, each child has a different chance of developing hereditary spherocytosis. Specifically, they have a 25% chance of developing the condition, a 50% chance of being a carrier but not developing the condition, and a 25% chance of avoiding being a carrier and having hereditary spherocytosis.

What happens when these genes mutate?

All cells have a membrane that separates their inside contents from the outside environment and protects them from that environment. Red blood cell membranes consist of a layer of thin outer membrane. Proteins connect the outer membrane to an inner membrane cytoskeleton.

Red blood cells need to bend, twist and turn so they can squeeze through narrow blood vessels and slide through your spleen. Red blood cells can fold down to one-third of the size of their surface. (Think of folding a soft shirt into small sections so it fits into an already-full suitcase.) The red cell membrane lets red blood cells keep their distinctive shape — a concave disk — but change shape as needed.

In hereditary spherocytosis, genetic mutations affect the red cell membrane proteins, breaking the connection between the cytoskeleton and the outer layer. The broken connection means the cytoskeleton can’t support the outer layer. As a result, red blood cells change from flexible disks to inflexible spherocytes.

How do healthcare providers diagnose hereditary spherocytosis?

Healthcare providers diagnose the condition by evaluating your symptoms, asking questions about your medical history and biological family medical history, and by doing several tests. This test may include:

• Complete blood count (CBC):This test gives healthcare providers information about your blood and overall health.
• Peripheral blood smear:Healthcare providers do this test to examine your blood cells’ size and shape.
• Reticulocyte count: Healthcare providers measure reticulocytes to find out if your bone marrow is producing enough healthy red blood cells.
• Direct antiglobulin (Coombs) test: This test checks for autoimmune hemolytic anemia.
• Bilirubin level: This is a blood test to check for high bilirubin levels.
• Red cell osmotic fragility: This test detects whether red blood cells are likely to break down.
• Plasma membrane electrophoresis: This is a technique that uses gel or fluid on an electric field to identify DNA, RNA or proteins. Healthcare providers use this test to identify which red cell membrane protein has mutated or changed.

How do healthcare providers treat hereditary spherocytosis?

Treatment varies depending on symptoms. For example, newborns who have severe anemia may receive blood transfusions and/or erythropoietin-stimulating agents (ESA) as soon as healthcare providers diagnose hereditary spherocytosis. ESA is a medication that encourages red blood cell production. Other potential treatments include:

• Phototherapy: Light treatment for jaundice in newborns.
• Blood transfusions: Healthcare providers may treat anemia with blood transfusions.
• Splenectomy: This is surgery to remove your spleen. Healthcare providers may treat severe forms of hereditary spherocytosis by removing your spleen.
• Gallbladder removal (cholecystectomy): This surgery treats gallstones.
• Iron chelation therapy: People who have blood transfusions may develop iron overload (hemochromatosis). Iron chelation therapy removes extra iron.

How can I prevent hereditary spherocytosis?

If you have a biological family history of the condition, you may not be able to prevent it. But it’s important to remember you and/or your children won’t necessarily develop hereditary spherocytosis just because you have a biological family history of it.

For example, if you inherited a mutated gene from one of your biological parents, there’s a 50% chance you’ll have hereditary spherocytosis. If you inherited mutated genes from both parents, there’s a 25% chance you’ll have the condition. There’s also a 50% chance you’ll carry the gene but never have hereditary spherocytosis.

If you’re concerned about your biological family history, ask your/your child’s healthcare provider about hereditary spherocytosis tests. The results will show whether you or your child inherited mutated genes. That way, you’ll be able to know what to expect.

Your healthcare provider will explain what test results mean, including whether you or your child have mild, moderate or severe forms of hereditary spherocytosis. They may have enough information to tell what medical conditions you or your child may develop, including the conditions’ early signs and symptoms.

What can I expect if I have/my child has this condition?

Most people who have heredity spherocytosis have a good prognosis, or expected outcome. Everyone’s situation is different. Your or your child’s prognosis depends on factors such as what form of hereditary spherocytosis you have or your child has and what other medical conditions you or your child have or had, as well as your/your child’s overall health.

My child has hereditary spherocytosis. How do I take care of them?

Children who have this condition will need regular follow-up visits so their healthcare providers can check on their overall health and look for any new signs or symptoms, including anemia or gallstones. If your child needed regular blood transfusions, healthcare providers may recommend your child be vaccinated against the hepatitis B virus. They may recommend steps you can take to protect your child from viral infections, particularly parvovirus B19, that can develop sudden and serious medical issues.

A note from Cleveland Clinic

Hereditary spherocytosis is a rare inherited disorder that requires lifelong medical care. Healthcare providers can treat the sometimes-serious medical conditions that hereditary spherocytosis causes. They can’t cure the blood disorder, though. It’s not always easy to have a chronic illness or care for someone who does. It may be harder still to live with an illness few people have or even know exists. If you have or your child has hereditary spherocytosis, you may feel overwhelmed, isolated and not sure where to turn for answers and support. Consider talking to your healthcare provider. They’re doing everything they can to help you and your child. They’ll be glad to answer your questions.