Hereditary spherocytosis is a genetic blood disorder characterized by the production of abnormally shaped red blood cells. These cells, known as spherocytes, are less flexible and more fragile than typical red blood cells. The condition is passed down through families due to alterations in specific genes, impacting red blood cell function.
Understanding Hereditary Spherocytosis
Hereditary spherocytosis affects the red blood cells, which are normally disc-shaped and flexible, allowing them to navigate through narrow blood vessels. In individuals with this condition, genetic changes result in defects in the proteins that form the red blood cell membrane. This structural weakness causes the cells to lose their biconcave shape and become spherical.
These rigid spherocytes are more susceptible to premature destruction, particularly as they pass through the spleen. The spleen acts as a filter, trapping and breaking them down at an accelerated rate. This increased destruction leads to hemolytic anemia, causing symptoms such as fatigue, pallor, and jaundice (a yellowing of the skin or eyes).
How Hereditary Spherocytosis is Inherited
Hereditary spherocytosis primarily follows two distinct patterns of inheritance: autosomal dominant and autosomal recessive. The specific pattern depends on the altered gene and its effect on red blood cell proteins.
Autosomal dominant inheritance is the most common form, accounting for about 75% of cases. In this pattern, an individual only needs one copy of an altered gene from one parent to develop the condition. If a parent has autosomal dominant hereditary spherocytosis, there is a 50% chance their child will inherit the altered gene and the disorder. This means that the condition often appears in every generation of an affected family.
Autosomal recessive inheritance is less frequent, accounting for roughly 25% of cases. For a child to develop hereditary spherocytosis through this pattern, they must inherit two copies of an altered gene, one from each parent. Parents are typically carriers, each having one altered gene copy without showing symptoms. When two carriers have children, there is a 25% chance the child will inherit two altered gene copies and be affected. There is also a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two unaffected gene copies and not be a carrier.
Genes Associated with Hereditary Spherocytosis
Hereditary spherocytosis results from changes in genes producing proteins that maintain red blood cell membrane structure and stability. Several genes have been identified, with alterations leading to varying severity and inheritance patterns. These genes encode proteins forming the red blood cell cytoskeleton, a network providing flexibility and durability.
The ANK1 gene, which codes for Ankyrin-1, is frequently implicated in autosomal dominant forms of the disorder. Ankyrin-1 helps anchor the red blood cell membrane to its underlying cytoskeleton. Alterations in SPTB, the gene for Beta-spectrin, are also a common cause of autosomal dominant hereditary spherocytosis. Beta-spectrin is a primary component of the red blood cell’s structural scaffold, and defects impair membrane integrity.
Another significant gene is SLC4A1, which codes for Band 3 protein, a major transmembrane protein involved in ion transport and support. Mutations in SLC4A1 can lead to both autosomal dominant and, less commonly, autosomal recessive forms of the condition. The EPB42 gene, encoding Protein 4.2, connects membrane proteins to the cytoskeleton. Alterations in EPB42 are associated with autosomal recessive inheritance. Finally, the SPTA1 gene, producing Alpha-spectrin, can be affected, often with an autosomal recessive pattern.
Genetic Testing and Family Planning
Genetic testing confirms hereditary spherocytosis and identifies the specific gene alteration. It involves analyzing a blood sample for mutations in associated genes. Pinpointing the genetic change provides valuable information about inheritance patterns and can predict severity.
Genetic counseling is a resource for individuals and families affected by hereditary spherocytosis. Genetic counselors explain inheritance patterns, assess the risk of passing the condition on, and discuss testing options. They help families understand the implications of genetic test results and make informed decisions about their health and family planning.
For couples at increased risk of having a child with hereditary spherocytosis, especially those with a known genetic mutation, family planning options exist. Prenatal diagnosis, such as amniocentesis or chorionic villus sampling, can test a fetus for the gene alteration. Preimplantation genetic diagnosis (PGD) is another option, used with in vitro fertilization, testing embryos for the genetic mutation before implantation. These options allow prospective parents to make choices based on comprehensive genetic information.