Hereditary spherocytosis is a genetic condition. In most cases it is inherited from a parent. Learn how HS is inherited and what happens in a de novo mutation.
Key points
Hereditary spherocytosis (HS) is an inherited blood disorder of the red blood cells.
HS affects approximately 1 in 2000-3000 people. The number of cases may be higher as mild cases can go undiagnosed.
A person can inherit HS through an autosomal dominant inheritance, autosomal recessive inheritance, or a de novo mutation. A de novo mutation occurs by chance and is not inherited from either parent.
Introduction
What is hereditary spherocytosis?
Hereditary spherocytosis (HS) is a genetic blood disorder of the red blood cells. Red blood cells contain hemoglobin, which is the molecule that carries oxygen from the lungs to the rest of the body.
Red blood cells are usually shaped like a disk, with a depressed centre, like a donut without a hole. In HS, most red blood cells are circular and shaped like spheres. These are called spherocytes.
HS is the most common form of inherited hemolytic anemia. “Hemolytic” refers to hemolysis, which is the breakdown of the red blood cells. Anemia is a lack of either hemoglobin or red blood cells in the body.
Causes, risk factors and prevalence
How is hereditary spherocytosis inherited?
In most cases, HS is an inherited genetic condition, which means that the genes involved in HS are typically passed down from one or both parents to their children.
Although HS occurs in all racial groups, it is more common in people of Northern European descent. HS affects approximately 1 in 2000-3000 people. The number of cases of HS may be underestimated because mild cases can go undiagnosed.
A gene is a section of DNA that gives specific instructions to a cell. Most of the time, the instruction is a recipe for making a protein. A change (mutation) in a gene results in a protein that cannot function properly.
In general, each person has two copies of every gene. One copy is inherited from the mother and the other from the father. There are three possible ways a person can inherit HS.
Autosomal dominant inheritance
Autosomal dominant inheritance occurs when one parent is affected with HS and the other parent is unaffected. One normal gene from the unaffected parent, and one gene with a mutation from the affected parent, are passed down to the child. In autosomal dominant inheritance, only one abnormal copy of the gene is needed to cause disease. A parent affected with HS has a 50% chance of passing the condition on to the child.
Autosomal dominant inheritance
Autosomal dominant inheritance occurs in approximately 70% to 80% of HS cases.
Autosomal recessive inheritance
In autosomal recessive inheritance both copies of the gene passed down to a child are abnormal and result in HS. In this scenario, both copies of the gene need to have a mutation to cause disease. Parents usually show no signs or symptoms of the disease as they typically have one normal copy of the gene and one abnormal copy of the gene (they are known as “carriers”).
Autosomal recessive inheritance
Autosomal recessive inheritance occurs in approximately 10% of HS cases.
De novo mutation
HS can be caused by a new (de novo) mutation that occurred by chance when the baby was conceived. It was not passed down from either parent.
De novo mutation
De novo mutations occur in approximately 20% of HS cases, however the exact number of de novo mutations in HS is not known.
