Fabry disease is a rare genetic disorder that affects various organs and systems in the body. It is a type of lysosomal storage disorder, which means that certain fatty substances accumulate in the cells, causing a range of symptoms and complications.
In this article, we will explore the causes and effects of Fabry disease and understand how it affects individuals.
What Causes Fabry Disease?
Fabry disease is caused by mutations in the GLA gene, which provides instructions for making an enzyme called alpha-galactosidase A (α-GAL A).
This enzyme is responsible for breaking down a fatty substance called globotriaosylceramide (Gb3) or ceramide trihexoside. In individuals with Fabry disease, mutations in the GLA gene lead to a deficiency or absence of α-GAL A enzyme activity, resulting in the accumulation of Gb3 in various tissues throughout the body.
Inheritance Patterns
Fabry disease is inherited in an X-linked recessive manner, which means that the gene mutation is located on the X chromosome. Since men have only one X chromosome, a single copy of the mutated gene is sufficient to cause the disease in males.
On the other hand, women have two X chromosomes, and thus, they need to inherit two copies of the mutated gene to develop the disease. However, in some cases, women with only one mutated copy of the gene may exhibit mild symptoms.
Effects of Fabry Disease on the Body
Fabry disease affects various organs and systems in the body, including the skin, kidneys, heart, and nervous system. The symptoms and severity of the disease can vary widely among affected individuals, even within the same family.
Skin Symptoms
One of the earliest signs of Fabry disease is skin involvement. Affected individuals may develop a reddish-purple rash called angiokeratomas, which typically appears in the groin area, buttocks, or umbilicus.
These skin lesions may also occur on the legs, arms, and torso. Angiokeratomas do not cause any physical discomfort but their presence can help in identifying Fabry disease.
Kidney Complications
Fabry disease can lead to progressive kidney damage. The accumulation of Gb3 in the cells of the kidneys can damage the delicate structures responsible for filtering waste products from the blood.
Over time, this can result in kidney dysfunction, characterized by proteinuria (presence of excess protein in the urine), declining renal function, and eventually, end-stage renal disease (ESRD) requiring dialysis or kidney transplant.
Cardiac Manifestations
The heart can also be affected by Fabry disease.
Gb3 deposition in the heart muscle can lead to various cardiovascular abnormalities, such as left ventricular hypertrophy (thickening of the heart walls), arrhythmias (irregular heart rhythms), and valve abnormalities. These cardiac complications can cause shortness of breath, chest pain, palpitations, and can eventually lead to heart failure.
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How Fabry Disease Affects the Body
Neurological Involvement
Fabry disease can also impact the central and peripheral nervous systems. The accumulation of Gb3 in nerve cells can result in neuropathic pain, which is often described as a burning or shooting sensation in the hands and feet.
Some individuals may also experience decreased sweating, dizziness, and problems with heat and cold tolerance. In severe cases, stroke and transient ischemic attacks (mini-strokes) can also occur.
Other Effects
In addition to the major organ systems mentioned above, Fabry disease can also have effects on other parts of the body. Some individuals may experience gastrointestinal symptoms, such as abdominal pain, diarrhea, or constipation.
Hearing loss and tinnitus (ringing in the ears) can also occur. Moreover, the disease can affect the eyes, leading to corneal opacity and reduced vision in some individuals.
Diagnosis and Treatment
Diagnosing Fabry disease can be challenging due to its wide range of symptoms and the rarity of the condition. However, early diagnosis is crucial for optimal management and treatment.
Diagnostic tests may include measuring α-GAL A enzyme activity or identifying specific gene mutations using DNA testing.
Although there is currently no cure for Fabry disease, there are treatment options available to manage the symptoms and slow down disease progression.
Enzyme replacement therapy (ERT) is the primary treatment approach, which involves intravenous infusion of synthetic α-GAL A enzyme to help break down Gb3 in the body. ERT has shown to improve various symptoms and slow the decline in kidney function and heart problems.
Living with Fabry Disease
Fabry disease is a chronic condition that requires lifelong management.
Along with medical treatments, individuals with Fabry disease can benefit from a multidisciplinary approach that includes regular monitoring of organ function, medications to control symptoms, and genetic counseling for family planning. Lifestyle modifications, such as maintaining a healthy diet, staying physically active, and avoiding triggers for pain episodes, can also contribute to overall well-being.
Conclusion
Fabry disease is a rare genetic disorder caused by mutations in the GLA gene, resulting in a deficiency of the α-GAL A enzyme. The disease can affect various organs and systems in the body, leading to a range of symptoms and complications.
Early diagnosis, genetic counseling, and appropriate management strategies are crucial in improving the quality of life for individuals with Fabry disease.
