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**IMPORTANT**
It is possible that the main title of the report (Hereditary Spherocytic Hemolytic Anemia) is not the name you expected. Please check the SYNONYMS listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms
Acholuric Jaundice
Chronic Acholuric Jaundice
Congenital Hemolytic Anemia
Congenital Hemolytic Jaundice
Congenital Spherocytic Anemia
Hereditary Spherocytosis
HS
Icterus (Chronic Familial)
Minkowski-Chauffard Syndrome
SPH2
Spherocytic Anemia
Spherocytosis


Disorder Subdivisions:


Information on the following diseases can be found in the Related Disorders section of this report:

Hereditary Nonspherocytic Hemolytic Anemia
Thalassemia Major
Thalassemia Minor
Anemias (General)



General Discussion
**REMINDER**
The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more detailed information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section this report.

Hereditary Spherocytic Hemolytic Anemia is a rare blood disorder characterized by defects within red blood cells (intracorpuscular) that result in a shortened survival time for these cells. Red blood cells (erythrocytes) normally circulate for a few months and when they die off are replaced by new erythrocytes. However, in Hereditary Spherocytic Hemolytic Anemia, the cells die prematurely. They also have low amounts of fats (lipid) in the cell membranes and an abnormally small amount of surface area. The red blood cells are sphere shaped (spherocytic) making it difficult for them to pass through the spleen, resulting in the early destruction of these cells (hemolysis). The sphere shape of the red blood cells is the hallmark of Hereditary Spherocytic Hemolytic Anemia, and this abnormality may be identified under a microscope. Hereditary Spherocytic Hemolytic Anemia is caused by an inherited metabolic defect.

Symptoms
Hereditary Spherocytic Hemolytic Anemia may be present at birth or may not become apparent for years. The symptoms of this disorder vary greatly from one person to another. In many people the symptoms are so mild that the disease is not diagnosed.

Symptoms of Hereditary Spherocytic Hemolytic Anemia may include excessive tiredness and a moderate persistent yellow appearance to the skin (jaundice). The onset of puberty may be delayed in children with Hereditary Spherocytic Hemolytic Anemia. Some children may experience abdominal discomfort and have an abnormally enlarged spleen (splenomegaly).

An infection is the most common cause of the temporary failure of the bone marrow to produce blood components (aplastic crisis) in people with Hereditary Spherocytic Hemolytic Anemia. This crisis results in a temporary deficiency of red blood cell production. Trauma or pregnancy may make the aplastic crisis worse. Symptoms of an aplastic crisis may include fever, headache, abdominal pain, profound loss of appetite (anorexia), vomiting, and fatigue. Children who are experiencing an aplastic crisis may also have nose bleeds (epistaxis).

Occasionally children with Hereditary Spherocytic Hemolytic Anemia have an abnormally enlarged liver (hepatomegaly), stones in the gall bladder (cholelithiasis), and/or leg ulcers. In some cases deformities of the anatomy are present at birth and may include more than the normal number of fingers and/or toes (polydactylism), and/or a "tower-shaped" skull.

Hemolytic Anemias, including Hereditary Spherocytic Hemolytic Anemia, have two distinct laboratory findings: a reduction in the life span of red blood cells and the retention of iron within the body particularly in those cells that have the ability to dispose of wastes and toxins (reticuloendothelial system or RES). In all hemolytic anemias, there is excessive destruction of red blood cells.

Causes
Hereditary Spherocytic Hemolytic Anemia is an inborn error of metabolism that can be inherited as an autosomal dominant or autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

The more severe forms of Hereditary Spherocytic Hemolytic Anemia are inherited as autosomal recessive genetic traits. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Usually people with Hereditary Spherocytic Hemolytic Anemia have a family history of anemia, jaundice, or spleen enlargement (splenomegaly). At times, other family members can be identified with this disorder, but in other cases people with Hereditary Spherocytic Hemolytic Anemia may have no family history of the disorder that can be traced.

The symptoms of Hereditary Spherocytic Hemolytic Anemia develop due to the abnormality of the red blood cell membrane. The defective gene that causes Hereditary Spherocytic Hemolytic Anemia is located on the short arm of chromosome 8.

Affected Population
Hereditary Spherocytic Hemolytic Anemia is a rare disorder that affects males and females in equal numbers. This disorder occurs most frequently in people of Northern European heritage with a prevalence of approximately 1 in 5,000 people. However, this disorder also occurs in other populations at a lower prevalence rate.



Related Disorders
Symptoms of the following disorders can be similar to those of Hereditary Hemolytic Spherocytic Anemia. Comparisons may be useful for a differential diagnosis:

Hereditary Nonspherocytic Hemolytic Anemia is a group of rare inherited blood disorders characterized by defective red blood cells that are not sphere-shaped. Symptoms may include moderate anemia, recurrent yellow appearance to the skin (jaundice), and an abnormally large spleen (splenomegaly) and/or liver (hepatomegaly). These symptoms usually occur in childhood. (For more information on this disorder, choose "Hereditary Hemolytic Nonspherocytic Anemia" as your search term in the Rare Disease Database.)

Thalassemia Major is a rare blood disorder characterized by a marked increase in F hemoglobin and a decrease in the production of certain oxygen carrying proteins in red blood cells. The symptoms of this disorder typically occur very suddenly in infancy or early childhood. These may include generalized weakness (malaise), an upset stomach (dyspepsia), and/or heart palpitations. Children may have a yellow appearance to their skin (jaundice), leg ulcers, and/or an abnormally enlarged liver (hepatomegaly) or spleen (splenomegaly). (For more information on this disorder, choose "Thalassemia Major" as your search term in the Rare Disease Database.)

Thalassemia Minor is a relatively mild form of anemia that is typically present at birth. It is inherited as an autosomal recessive genetic trait. Constant fatigue may be the only symptom of this disorder. However, if anemia becomes severe, the spleen may become slightly enlarged (splenomegaly) and there may be a pale color to the skin. Occasionally a child with Thalassemia Minor may complain of pain in the left upper side of the abdomen. This disorder may be aggravated by stress, infections, malnutrition, and/or pregnancy. (For more information on this disorder, choose "Thalassemia Minor" as your search term in the Rare Disease Database.)

Spherocytic red blood cells may also occur in Hemoglobin C Disease, drug induced Hemolytic Anemias, and in people who have alcoholism. They may also be present in individuals who experience serious burns on their bodies.

Other types of anemias include: Aplastic Anemia, Megaloblastic Anemia, Warm Antibody Hemolytic Anemia, Cold Antibody Hemolytic Anemia, Acquired Autoimmune Hemolytic Anemia, Pernicious Anemia, Folic Acid Deficiency Anemia, Blackfan-Diamond Anemia, Sickle Cell Anemia, and Fanconi's Anemia. (For information on other types of Anemias, choose "Anemia" as your search term in the Rare Disease Database.)

Standard Therapies
Hereditary Spherocytic Hemolytic Anemia usually has a long, chronic course. The only currently recognized specific treatment for this disorder is the removal of the spleen (splenectomy). This surgery is typically performed in an individual with this disorder who is under the age of 45 years and has had jaundice, ongoing pain in the upper right abdomen (biliary colic), and a number of aplastic crises. Removal of the spleen should be avoided in children under age 5 years because of the risk of overwhelming bacterial infection. Following the surgery the symptoms typically disappear.

During an aplastic crisis, a person with Hereditary Spherocytic Hemolytic Anemia should seek immediate medical attention. Blood transfusions may be necessary to prevent the collapse of the cardiovascular system. If the crisis is the result of an infection, antibiotic treatment may be necessary.

Genetic counseling will be of benefit for people with Hereditary Spherocytic Hemolytic Anemia and their families. Other treatment is symptomatic and supportive.



Investigational Therapies
Studies are being conducted in the use of immunoglobulin (human) as a treatment for Hereditary Spherocytic Hemolytic Anemia. Further investigation is needed to determine the long-term safety and effectiveness of this treatment.



This disease entry is based upon medical information available through February 1998. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

Resources

This information was provided by the National Organization for Rare Disorders, P.O. Box 8923, New Fairfield, CT 06812-8923, phone: (203) 746-6518, web site: www.rarediseases.org, e-mail: orphan@rarediseases.org.

For more information on Anemia, Hereditary Spherocytic Hemolytic, please contact:

March of Dimes Birth Defects Foundation
1275 Mamaroneck Avenue
White Plains, NY 10605
(914) 428-7100
(888) 663-4637
e-mail: resourcecenter@modimes.org
Home Page: http://www.modimes.org



NIH/National Heart, Lung and Blood Institute
31 Center Drive MSC 2480
Building 31A Rm 4A16
Bethesda, MD 20892--2480
(301) 592-8573
e-mail: nhlbiinfo@rover.nhlbi.nih.gov
Home Page: http://www.nhlbi.nih.gov/







References
MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1025-28, 1702.

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., Editors; McGraw Hill, 1989. P. 362.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 858-860.

THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 1167, 1999.

HEMATOLOGY, 4th Ed,: William J. Williams, et al., Editors; McGraw-Hill, Inc., 1990. Pp. 558-569.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 1573-75.

HOMOZYGOSITY FOR DOMINANT FORM OF HEREDITARY SPHEROCYTOSIS. F. Duru; Br J Heamotol (Nov 1992; 82(3)). Pp. 596-600.

CURRENT PROBLEMS IN HAEMATOLOGY. 2: HEREDITARY SPHEROCYTOSIS. J.C. Smiley; J Clin Pathol (Jun 1991; 44(6)). Pp. 441-44.

SPLENIC SEQUESTRATION ASSOCIATED WITH SICKLE CELL TRAIT AND HEREDITARY SPHEROCYTOSIS. Y.M. Yang; Am J Hematol (Jun 1992; 40(2)). Pp. 110-6.


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