Hereditary spherocytosis

What causes hereditary spherocytosis?

Hereditary spherocytosis may be caused by changes (mutations) in any of several genes. These genes give the body instructions to make proteins that exist on the membranes of red blood cells. These proteins carry molecules in and out of cells, keep cell structure, and attach to other proteins. Some increase the flexibility of cells so they can easily travel from larger blood vessels to smaller, narrow blood vessels.

The gene mutations that cause hereditary spherocytosis cause red blood cells to have an abnormal, spherical shape with decreased flexibility. The misshapen red blood cells are called spherocytes. The spherocytes are taken out of circulation and sent to the spleen to be destroyed (hemolysis). This results in a shortage of red blood cells in the blood, and too many in the spleen.

About half of all cases of hereditary spherocytosis are due to mutations in the ANK1 gene. Other genes associated with the condition include the EPB42, SLC4A1, SPTA1 , and SPTB genes.

Last updated on 05-01-20

Can hereditary spherocytosis be caused by radiation or drug exposure?

Currently there is no evidence to suggest that radiation or drug exposure causes hereditary spherocytosis.

Last updated on 05-01-20

How is hereditary spherocytosis inherited?

About 75% of cases of hereditary spherocytosis are inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Less commonly, hereditary spherocytosis is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

  • 25% (1 in 4) chance to be affected
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not be a carrier

In some of the cases that result from new mutations in people with no family history of the condition, the inheritance pattern may be unclear.

Last updated on 05-01-20

Does hereditary spherocytosis increase the risk of stroke or heart attack?

Very rarely, hereditary spherocytosis (HS) in people that have not undergone splenectomy has been associated with Moyamoya disease, which can increase the risk of blood clots, strokes, and transient ischemic attacks. However, because people who are anemic have lower cholesterol and whole blood viscosity than those who are not anemic, it has been suggested that people with HS who have not had their spleen removed should have fewer arteriosclerotic events (such as heart attack or stroke) than unaffected family members. Chronic anemia may slow down the development of arteriosclerosis.

People with HS who have undergone splenectomy may be at increased risk. Both venous and arterial vascular events have been associated with HS in patients who have undergone splenectomy compared to non-splenectomized patients. Long-term potential complications of splenectomy in adults may include an increased risk of atherosclerotic heart disease, and many adults who have had a splenectomy are on a low-dose aspirin therapy regimen. More recently, some evidence has pointed to a connection between splenectomy for HS and the development of venous thrombosis (blood clots). In some cases, a high platelet count has been suggested as a contributing factor. In others, the connection is less clear. In some patients, pulmonary hypertension has developed related to blood clots in the lung.

Last updated on 05-01-20

How might splenectomy affect pregnancy?

Few studies have investigated the effect of splenectomy on pregnancy. Most of the studies performed looked at neonatal outcome among women with immune thrombocytopenia (ITP) who have had a splenectomy, and very few have focused on obstetric outcome.

A study that investigated pregnancy in patients with hereditary spherocytosis (HS) found that only about one third of pregnancies in non-splenectomized women developed anemia, or anemia deteriorated. The authors noted that in splenectomized patients, the incidence of complaints was minimal.

There has been one retrospective study comparing pregnancies of women who have and have not undergone splenectomy (not specific to women with HS). The major finding of this study was that splenectomy is a significant risk factor for adverse obstetric outcomes, and specifically, is an independent risk factor for preterm delivery. However, while there were higher rates of preterm delivery, these deliveries were near term and had no impact on birth outcome.

Obstetric complications associated with splenectomy included C-section, maternal blood transfusion, pneumonia during pregnancy, and unspecified complications of anesthesia and sedation during labor. Higher rates of fertility treatments were also found among post-splenectomy women.

Importantly, pregnancies following splenectomy were not associated with adverse perinatal outcome - no significant differences were found between the groups regarding low Apgar scores, congenital malformations (birth defects), intrauterine growth restriction (IUGR), or perinatal death.

Last updated on 05-01-20

Is there a particular diet that is recommended for children with hereditary spherocytosis?

We are not aware of specific diet recommendations for children with hereditary spherocytosis, however folic acid supplements may be recommended in some cases (for example in young children who have not undergone spleenectomy). The folic acid may help your child's body produce red blood cells. We recommend that you talk to your son's doctor about folic acid supplements and his diet.

Last updated on 05-01-20

What are the current recommendations regarding post-splenectomy antibiotic prophylaxis in children?

The ideal duration of antibiotic prophylaxis for children is not clear. Recommendations for daily prophylaxis differ among different authorities. Guidelines in the United States suggest relatively limited courses of post-splenectomy prophylaxis (up to five years of age and for at least one year after splenectomy), whereas British guidelines recommend lifelong penicillin prophylaxis in high- risk individuals (defined as those less than 16 or more than 50 years of age, and those with an inadequate response to pneumococcal vaccination).

The American Academy of Pediatrics Committee on Infectious Diseases published a policy statement in 2000 which included the following information:

  • Antibiotic prophylaxis is recommended for all children with sickle cell disease (SCD) and functional or anatomic asplenia, regardless of whether they have received pneumococcal immunizations.
  • Although the efficacy of penicillin prophylaxis in children with functional or anatomic asplenia other than SCD has not been studied, it is reasonable to use prophylaxis in the same regimen.
  • Antibiotic prophylaxis should be begun before 2 months of age or as soon as SCD or asplenia occurs or is otherwise recognized or suggested by screening procedures.
  • Oral administration of penicillin V potassium is recommended at a dosage of 125 mg twice a day until 3 years of age and at a dosage of 250 mg twice a day after 3 years of age.
  • Children who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations may discontinue penicillin prophylaxis after 5 years of age.

It has also been stated that individuals in whom prophylaxis is being discontinued should have well-established, regular medical care, and understand the warning symptoms and signs, as well as the management, of possible post-splenectomy sepsis. Individuals with highly compromised immune systems, and survivors of pneumococcal post- splenectomy sepsis, are reasonable candidates for prophylaxis until age 18, or even for life.

Individuals looking for specific medical advice for themselves or family members should speak with their health care provider.

Last updated on 05-01-20

Can my unaffected children pass hereditary spherocytosis on to their children?

The offspring of an individual affected with an autosomal dominant (AD) form of hereditary spherocytosis has a 50% (1 in 2) risk to inherit the same mutation in the disease-causing gene. If a child of an affected parent with AD hereditary spherocytosis does not inherit the mutation, that child will not pass the mutation on to his/her children because it is not present in his/her genes.

The offspring of an individual with an autosomal recessive (AR) form of hereditary spherocytosis will definitely be a carrier of the condition. A carrier of an AR condition is generally only at risk to have an affected child if his/her partner is also a carrier for the condition, having a mutation in the same disease-causing gene. When 2 carriers of an AR condition have children, each child has a 25% (1 in 4) risk to be affected. If a carrier has a child with an individual who is not a carrier, that child will not be affected.

Last updated on 05-01-20

What is Soliris?

Soliris is a drug that has been FDA approved to treat paroxysmal nocturnal hemoglobinuria (PNH). PNH causes the early death and impaired production of blood cells (red blood cells, white blood cells, and platelets). This early destruction of blood cells occurs because the affected cells are missing two important proteins, making them vulnerable to destruction by a part of our immune system called the complement system. Soliris works by blocking the complement system. You can learn more about Soliris by visiting the DailyMed.gov Web page on this topic.

Last updated on 05-01-20

Can Soliris be used to treat hereditary spherocytosis?

Currently, we are not aware of any benefits of Soliris for treating hereditary spherocytosis. The destruction of red blood cells in this condition is a result of mishapen and fragile cell membranes.

Last updated on 05-01-20

Is splenectomy or gallbladder removal for hereditary spherocytosis associated with chronic, excessive fatigue?

Fatigue may be a symptom of hereditary spherocytosis (HS), and is often associated with anemia in affected people. However, splenectomy typically cures the anemia (improving associated symptoms) in people with HS. Some people with severe HS may remain anemic post-splenectomy, and may need blood transfusions during an infection. We are not aware of reports in the literature suggesting that splenectomy or gallbladder removal is associated with persistent or excessive fatigue years after undergoing these surgeries.

Fatigue can be an important sign of many different types of illnesses or underlying conditions. We are unable to say whether it may be associated with hereditary spherocytosis, splenectomy, or gallbladder removal in any specific case. Fatigue that impacts daily life activities, or affects emotional or psychological well-being, should be discussed with a healthcare provider, as it may require medical treatment.

Last updated on 05-01-20

How might hereditary spherocytosis affect pregnancy?

There is limited information about the effect of hereditary spherocytosis (HS) on pregnancy. Hemolytic crisis and persistent anemia have been reported during pregnancy, especially in women who have not undergone splenectomy.

One article reported on 8 patients with HS who had a total of 19 pregnancies:

  • 10 pregnancies occurred in patients before splenectomy, and 9 occurred after splenectomy.
  • There were 13 term births, 4 spontaneous abortions (miscarriages), and 2 therapeutic abortions (pregnancy termination for medical indications).
  • Of the 19 pregnancies, 8 were complicated by anemia and all were in patients without splenectomy. A hemolytic crisis occurred in 6 pregnancies, and persistent anemia occurred in 2 pregnancies. Transfusion was required in 4 pregnancies.

It would appear that pregnancy may cause hemolytic anemia, but maternal morbidity and fetal outcome seem more favorable after splenectomy than before splenectomy.

In terms of pregnancy management, folic acid supplementation is necessary. Monitoring for worsening of anemia with complete blood counts and reticulocyte counts is recommended.

Last updated on 05-01-20

Is activity restriction recommended for children with hereditary spherocytosis?

Doctors may recommend that children with hereditary spherocytosis (HS) avoid activities that could result in blunt injuries to the abdomen. This is to reduce the risk of injury to the spleen, which is often enlarged in people with HS. This remains an area of controversy however, since there is limited data demonstrating that people with HS are in fact at an increased risk for injury. People with hereditary spherocytosis may experience fatigue, exercise intolerance, and weakness. These symptoms and your son's activities should be discussed with your son's healthcare provider.

Last updated on 05-01-20

What are the long term effects of removal of spleen and gallbladder in children with hereditary spherocytosis?

Overall, individuals with hereditary spherocytosis (HS) who have had their spleen removed showed an improvement in quality of life..

Complete removal of the spleen (splenectomy) cures almost all patients with hereditary spherocytosis. The spleen, however, is important in fighting infection. Individuals, particularly children, who have had a splenectomy are more likely to contract a serious and possibly life-threatening infection (sepsis). Most septic infections have been observed in children whose spleens were removed in the first years of life, although older children and adults also are susceptible. Subtotal (partial) splenectomy is an effective alternative to total splenectomy; decreasing (but not eliminating) hemolysis (breakdown of red blood cells) and reducing the need for blood transfusions, while maintaining spleen function. Subtotal splenectomy, however, is not effective in preventing gallstone formation.

Gallbladder removal (cholecystectomy) is a procedure that has been shown to help prevent biliary tract disease and, in some patients with mild HS, helps avoid the need for splenectomy. Removal of the gallbladder has not been known to cause any long-term adverse effects, aside from occasional diarrhea.

Last updated on 05-01-20

What is hereditary spherocytosis?

Hereditary spherocytosis is a condition characterized by hemolytic anemia (when red blood cells are destroyed earlier than normal). Signs and symptoms can range from mild to severe and may include pale skin, fatigue, anemia, jaundice, gallstones, and/or enlargement of the spleen. Other symptoms of hemolytic anemia may include feeling that your heart is pounding or racing (palpitations), feeling dizzy, problems concentrating, and headaches. Some people with a severe form of hereditary spherocytosis may have short stature, delayed puberty, and skeletal abnormalities. The condition is caused by mutations in any of several genes, such as the ANK1, EPB42, SLC4A1, SPTA1 , and SPTB genes. It is most commonly inherited in an autosomal dominant manner, but may be inherited in an autosomal recessive manner. There are different types of hereditary spherocytosis, which are distinguished by severity and genetic cause. Depending on severity, treatment may involve splenectomy, red cell transfusions, folic acid supplementation, and/or cholecystectomy.

Last updated on 05-01-20

How can I learn about clinical trials and research studies involving new treatments for hereditary spherocytosis?

Clinical trials are medical research studies in which people participate as volunteers. They are a means of developing new treatments and medications for diseases and conditions. Studies may also focus on improving diagnostic techniques, investigating the cause of the condition or understanding how the condition changes throughout an affected person's lifetime. There are strict rules for clinical trials, which are monitored by the National Institutes of Health (NIH) and the U.S. Food and Drug Administration.

Please note: you do not have to be willing to enroll in a clinical trial to find this information helpful. Seeing what medications or new treatments are being tested in these studies can help you stay up to date on which new treatment options may be available in the future. Staying in touch with the advocacy groups can also help you stay up-to-date on both research and treatment options.

Some of the research studies at the NIH Clinical Center involve promising new treatments that may directly benefit patients. The Clinical Center does not charge patients for participation and treatment in clinical studies conducted at the NIH.

Studies conducted off campus at other hospitals, clinics or through pharmaceutical companies do bill your insurance for part of the cost of the trial, so it is always good to ask if you will be responsible for any of the cost of the study before volunteering.
ClinicalTrials.gov (developed by the National Institutes of Health through the National Library of Medicine) provides patients, family members, and members of the public with current information on clinical research studies.

You can view the current clinical trials enrolling people with hereditary spherocytosis. You can use the "Map" tab or "Modify Search" feature to limit your search to different states of the United States. Just click on a study to find out more information and if interested you can review the "eligibility" criteria to see if you can enroll. After you click on a study, review its "eligibility" criteria to determine its appropriateness. Use the study’s contact information to learn more. Check this site often for regular updates.

You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH) by calling 1-800-411-1222 to speak with a specialist, who can help you determine if you are eligible for any clinical trials.

Last updated on 05-01-20

How can I learn about research involving hereditary spherocytosis?

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. You can view information about clinical trials relating to hereditary spherocytosis here. Use the study’s contact information to learn more. Check this site often for regular updates.

You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH). We recommend calling 1-800-411-1222 to speak with a specialist, who can help you determine if you are eligible for any clinical trials. If you are located outside the United States, and would like to be contacted via telephone, you will need to contact PRPL and provide your telephone number in full, including area code and international dialing prefix.

Patient Recruitment and Public Liaison Office
NIH Clinical Center
Bethesda, Maryland 20892-2655
Toll-free: 1-800-411-1222
Fax: 301-480-9793
E-mail: prpl@mail.cc.nih.gov
Web site: http://clinicalcenter.nih.gov

You can find information about participating in a clinical trial as well as learn about resources for travel and lodging assistance, through the Get Involved in Research section of our Web site.

Last updated on 05-01-20

What is the long-term outlook for people with hereditary spherocytosis?

Overall, the long-term outlook (prognosis) for people with hereditary spherocytosis (HS) is usually good with treatment. However, it may depend on the severity of the condition in each person. HS is often classified as being mild, moderate or severe. People with very mild HS may not have any signs or symptoms unless an environmental "trigger" causes symptom onset. In many cases, no specific therapy is needed other than monitoring for anemia and watching for signs and symptoms. Moderately and severely affected people are likely to benefit from splenectomy. Most people who undergo splenectomy are able to maintain a normal hemoglobin level. However, people with severe HS may remain anemic post- splenectomy, and may need blood transfusions during an infection.

Information about life expectancy in the medical literature appears to be limited. However, we are not aware of reports that state that life expectancy is known to be significantly shortened in people without other medical problems who are managed appropriately. In all people who undergo splenectomy, there is a lifelong, increased risk of developing a life-threatening infection (sepsis). Although most septic episodes have been observed in children whose spleens were removed in the first years of life, older children and adults also are susceptible. Fortunately, taking certain precautions can reduce this risk and can prevent minor infections from becoming life- threatening.

Last updated on 05-01-20

How might hereditary spherocytosis be treated?

The treatment of hereditary spherosytosis (HS) is dependent on the severity of the condition and recommendations vary a bit in the medical literature. In general, folate therapy (a type of vitamin B to support red blood cell production) is recommended for those with moderate to severe anemia, although some doctors may also recommend it for those with mild anemia. Red blood cell transfusions may be required in severe cases of anemia, particularly in the first years of life or during infections and pregnancy. If red blood cell transfusions are needed repeatedly, iron chelating therapy may be required to reduce iron overload.

Regular monitoring for anemia and gallstones is advised. Removal of the spleen (splenectomy) is usually only performed in severe HS or in moderate to severe cases with significant anemia and gallstone complications. Splenectomy is not recommended in cases of mild HS except in specific cases. The majority of medical researchers no longer recommend that the spleen be removed during gallbladder removal (cholecystectomy), unless there are other reasons to do so. In some cases only removing of part of the spleen is advised. Expert evaluation is recommended in order to avoid unnecessary spleen removal.

Last updated on 05-01-20

Name: Hereditary Spherocytosis (HS) Support Group Phone: 201 487-6394 Email: jsommers@bergen.edu
Name: European Network for Rare and Congenital Anaemias (ENERCA) University of Barcelona Red Cell Pathology Unit
C/Villarroel, 170 - 08036 Barcelona
España
Phone: (34) 93 451 5950 Fax : (34) 93 227 1764 Email: enerca@enerca.org Url: http://www.enerca.org
Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ and General Haematology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis and management of hereditary spherocytosis British Journal of Haematology. January 2012; 156(1). 37-49. Reference Link

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