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 is 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 this disorder, and this abnormality may be identified under a microscope. Hereditary spherocytic hemolytic anemia is caused by an inherited metabolic defect.
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 this disorder. 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.
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 typical, common form of inheritance is autosomal dominant, although there are rare occurrences of autosomal-recessive forms.
Most cases of the autosomal-dominant form are due to defects of a protein known as ankyrin. These cases are associated with a gene located on the short arm of chromosome 8 (8p11.2).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many numbered bands. For example, “chromosome 8p11.2″ refers to band 11 on the short arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy, regardless of the sex of the resulting child.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, he or she will be a carrier of the disease, but usually will not show symptoms. The risk of two carrier parents both passing the defective gene and having an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance of having a child who receives normal genes from both parents and is genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than do unrelated parents of both carrying the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.
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 in that population. However, this disorder also occurs in other populations at a lower prevalence rate.
Hereditary spherocytic hemolytic anemia usually has a long, chronic course. The standard treatment is folic acid replacement so that adequate stores will be available to maintain increased red cell production. Red cell transfusions may be needed for times of profound anemia during aplastic crisis, or on a chronic basis for the severe forms. For severe neonatal jaundice, exchange transfusion may be required.
If patients have moderate to severe anemia and/or chronic jaundice, removal of the spleen (splenectomy) will usually nearly eliminate the symptoms of the autosomal-dominant condition and improve the symptoms in the more severe recessive forms. Surgical removal of the gallbladder (cholecystectomy) may be required to address the symptoms related to the gallstones.
Genetic counseling will be of benefit for families affected by hereditary spherocytic hemolytic anemia. Other treatment is symptomatic and supportive.
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Subtotal splenectomy and gene transfer are under investigation as possible treatments for this disorder.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:182300; Last Update:3/6/02.