Anderson-Fabry Disease
Description
Anderson-Fabry disease, also known as Fabry disease, is a rare genetic disorder that affects multiple organs in the body. It‘s caused by a deficiency in the enzyme alpha-galactosidase A, leading to the accumulation of a fatty substance called globotriaosylceramide (Gb3) in various tissues. This buildup can lead to a wide range of symptoms, impacting the heart, kidneys, nervous system, and skin.
Genes Involved
Anderson-Fabry disease is caused by mutations in the GLA gene, located on the X chromosome. This gene provides instructions for making the alpha-galactosidase A enzyme. Mutations in this gene lead to a deficiency or absence of the enzyme, resulting in the accumulation of Gb3.
Recognizing the Signs and Symptoms
The symptoms of Anderson-Fabry disease can vary depending on the severity of the condition and the age of onset. Common signs and symptoms include:
- Pain: A hallmark symptom, often described as burning, stabbing, or aching, particularly in the extremities, hands, and feet.
- Skin lesions: Red, raised spots (angiokeratomas) may appear on the skin, especially in the lower body.
- Kidney problems: Fabry disease can affect kidney function, leading to proteinuria (protein in the urine) and eventually kidney failure.
- Heart problems: Accumulation of Gb3 in the heart can lead to thickened heart walls, arrhythmias (irregular heartbeat), and heart valve problems.
- Nervous system issues: Fabry disease can affect the nervous system, causing numbness, tingling, and pain in the extremities, as well as cognitive decline.
- Eye problems: Opacities in the cornea (cloudy patches) and retinal lesions can occur.
- Hearing loss: Some individuals with Fabry disease may experience hearing loss.
- Gastrointestinal problems: Nausea, vomiting, and diarrhea are also possible symptoms.
Causes
The underlying cause of Anderson-Fabry disease is a genetic mutation in the GLA gene. This mutation is inherited in an X-linked recessive pattern, meaning that the gene is located on the X chromosome and females are carriers while males are affected. For a male to be affected, he needs to inherit the mutated gene from his mother. For a female to be affected, she needs to inherit the mutated gene from both parents.
Inheritance/recurrence risk
Anderson-Fabry disease is inherited in an X-linked recessive pattern. This means that the mutated gene is located on the X chromosome and females are carriers while males are affected. For a male to be affected, he needs to inherit the mutated gene from his mother. For a female to be affected, she needs to inherit the mutated gene from both parents.
The risk of inheriting the mutated gene from a carrier mother to a son is 50%. The risk of inheriting the mutated gene from a carrier mother to a daughter is also 50%, but the daughter will likely be a carrier unless she inherits the mutated gene from her father as well.
