Fabry disease is a rare genetic disorder that is indeed hereditary. It is caused by mutations in the GLA gene, which provides instructions for producing an enzyme called alpha-galactosidase A (α-Gal A). This enzyme is responsible for breaking down a fatty substance called globotriaosylceramide (Gb3) or globotriaosylsphingosine (Lyso-Gb3) in the body.
When a person inherits a mutated GLA gene from one or both parents, their body is unable to produce enough functional α-Gal A enzyme. As a result, Gb3 and Lyso-Gb3 accumulate in various cells and tissues, leading to the characteristic symptoms and complications of Fabry disease.
Inheritance Pattern:
Fabry disease follows an X-linked recessive inheritance pattern. This means that the gene responsible for the disorder is located on the X chromosome. Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY).
If a woman carries a mutated GLA gene on one of her X chromosomes, she is considered a carrier of Fabry disease. Carriers usually do not experience severe symptoms because they have a second X chromosome with a normal GLA gene that produces enough α-Gal A enzyme.
On the other hand, if a man inherits a mutated GLA gene on his single X chromosome, he will develop Fabry disease. Since males have only one X chromosome, they do not have a backup copy of the GLA gene to compensate for the faulty one.
Transmission of Fabry Disease:
When a carrier female and a non-affected male have children, there is a 50% chance that each of their daughters will be carriers and a 50% chance that each of their sons will inherit Fabry disease. This is because the daughter has a 50% chance of inheriting the mutated X chromosome from her carrier mother and a 50% chance of inheriting the unaffected X chromosome from her father.
When a man with Fabry disease has children with a non-affected female, all of their daughters will be carriers, but none of their sons will have the disease. This is because the father passes his single X chromosome (with the mutated GLA gene) to all of his daughters, while he passes his Y chromosome (without the GLA gene) to all of his sons.
Genetic Testing and Counseling:
If there is a family history of Fabry disease or if someone is experiencing symptoms suggestive of the condition, it is recommended to undergo genetic testing. Genetic testing can identify mutations in the GLA gene and confirm the diagnosis of Fabry disease.
Genetic counseling is also crucial for individuals and families affected by Fabry disease. A genetic counselor can provide information about the inheritance pattern, the risk of passing on the disease, and the available options for family planning.
Conclusion:
Fabry disease is a hereditary disorder caused by mutations in the GLA gene. It follows an X-linked recessive inheritance pattern, with carrier females and affected males. Genetic testing and counseling play a vital role in managing the condition and making informed decisions regarding family planning.