What are the other Names for this Condition? (Also known as/Synonyms)

• Congenital Spherocytosis
• HS (Hereditary Spherocytosis)
• Spherocytic Anemia

What is Hereditary Spherocytosis? (Definition/Background Information)

• 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. Some people with a severe form may have short stature, delayed sexual development, 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

(Source: Hereditary Spherocytosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hereditary Spherocytosis? (Age and Sex Distribution)

• Hereditary Spherocytosis is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hereditary Spherocytosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hereditary Spherocytosis is an inherited condition
• Currently, no risk factors have been clearly identified for this blood disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Spherocytosis? (Etiology)

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.

• 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
• 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
• 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

(Source: Hereditary Spherocytosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Autosomal dominant:

Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

• Autosomal recessive:

Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Hereditary Spherocytosis?

The signs and symptoms of Hereditary Spherocytosis may include:

• Cholelithiasis
• Hemolytic anemia
• Hyperbilirubinemia
• Jaundice
• Reticulocytosis
• Spherocytosis
• Splenomegaly

(Source: Hereditary Spherocytosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hereditary Spherocytosis Diagnosed?

Hereditary Spherocytosis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Spherocytosis?

The complications of Hereditary Spherocytosis may include:

• Delayed sexual growth
• Weak bones
• Formation of gallbladder stones

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hereditary Spherocytosis Treated?

The treatment of Hereditary Spherocytosis (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

(Source: Hereditary Spherocytosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Hereditary Spherocytosis be Prevented?

Currently, Hereditary Spherocytosis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hereditary Spherocytosis? (Outcomes/Resolutions)

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. Life expectancy is not 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

(Source: Hereditary Spherocytosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Hereditary Spherocytosis:

• Hereditary Spherocytosis is also known by the following names: Congenital Spherocytic Hemolytic Anemia

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/