Glucose-6-phosphate dehydrogenase
is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two
sex chromosomes
in each cell. Males he only one X chromosome and females he two copies of the X chromosome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In females, who he two copies of the X chromosome, one altered copy of the G6PD
gene in each cell can lead to less severe features of the condition or may cause no signs or symptoms at all. However, many females with one altered copy of this gene he glucose-6-phosphate dehydrogenase deficiency similar to affected males because the X chromosome with the normal copy of the G6PD
gene is turned off through a process called
X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, he only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.
Research shows that females with glucose-6-phosphate dehydrogenase deficiency caused by variants in the G6PD gene often he skewed X-inactivation, which results in the inactivation of the X chromosome with the normal copy of the G6PD gene in most cells of the body. This skewed X-inactivation causes the chromosome with the altered聽G6PD gene to be expressed in more than half of cells. As a result, not enough normal glucose-6-phosphate dehydrogenase enzyme is produced, leading to hemolytic anemia and other signs and symptoms of glucose-6-phosphate dehydrogenase deficiency.聽