Summary about Disease
Fabry disease is a rare, inherited lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A (α-Gal A). This deficiency leads to the buildup of a fatty substance called globotriaosylceramide (Gb3 or GL-3) in cells throughout the body. This accumulation can damage organs and tissues, leading to a variety of symptoms and complications. Fabry disease is an X-linked condition, meaning it is more common and often more severe in males than in females, although females can also experience significant symptoms.
Symptoms
Symptoms of Fabry disease can vary significantly in severity and presentation from person to person. Some common symptoms include:
Angiokeratomas: Small, dark red spots on the skin, often clustered around the belly button, groin, and thighs.
Acroparasthesia: Burning or tingling pain in the hands and feet. This pain can be episodic and triggered by stress, exercise, temperature changes, or illness.
Decreased sweating (hypohidrosis) or absent sweating (anhidrosis): Difficulty sweating, leading to overheating.
Gastrointestinal problems: Abdominal pain, diarrhea, constipation, nausea, and vomiting.
Eye abnormalities: Whorled corneal opacities (visible when examining the cornea of the eye).
Kidney problems: Proteinuria (protein in the urine), gradual decline in kidney function, and eventually kidney failure.
Heart problems: Enlarged heart (cardiomyopathy), irregular heart rhythms (arrhythmias), and increased risk of heart attack and stroke.
Neurological problems: Stroke, transient ischemic attacks (TIAs), vertigo, and hearing loss.
Fatigue: Persistent tiredness and lack of energy.
Causes
Fabry disease is caused by mutations in the GLA gene, which provides instructions for making the enzyme alpha-galactosidase A (α-Gal A). These mutations result in a deficiency or complete absence of α-Gal A. Without enough of this enzyme, globotriaosylceramide (Gb3) cannot be broken down effectively and accumulates in cells throughout the body. This accumulation damages cells and tissues, leading to the signs and symptoms of Fabry disease. Fabry disease is inherited in an X-linked pattern. Males inherit their single X chromosome from their mother. If the mother has a mutated *GLA* gene on one of her X chromosomes, there is a 50% chance that her son will inherit the mutated gene and develop Fabry disease. Females inherit one X chromosome from each parent. If a female inherits a mutated *GLA* gene on one X chromosome, she may or may not develop symptoms of Fabry disease. In some cases, females with one mutated *GLA* gene can be as severely affected as males.
Medicine Used
The primary treatment options for Fabry disease include:
Enzyme Replacement Therapy (ERT): ERT involves intravenous infusions of a manufactured version of the α-Gal A enzyme. This therapy helps to replace the missing enzyme and reduce the buildup of Gb3 in cells. Currently available ERT medications include agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme).
Chaperone Therapy: Migalastat (Galafold) is a chaperone therapy that works differently from ERT. It is a small molecule that binds to certain forms of the mutated α-Gal A enzyme, stabilizing it and allowing it to function more effectively. Migalastat is only approved for patients who have specific mutations in the GLA gene that are "amenable" to chaperone therapy.
Symptomatic Treatment: Medications and therapies to manage specific symptoms of Fabry disease, such as pain management for acroparasthesia, blood pressure control for kidney and heart problems, and gastrointestinal medications for digestive issues.
Supportive care: Other therapies may include kidney dialysis or kidney transplant for end-stage renal disease, pacemakers or other cardiac devices for heart rhythm abnormalities.
Is Communicable
Fabry disease is not communicable. It is a genetic disorder caused by a mutation in the GLA gene and cannot be spread from person to person through contact or any other means.
Precautions
Since Fabry disease is a genetic condition, precautions primarily involve:
Genetic Counseling: Individuals with Fabry disease or a family history of the disease should consider genetic counseling to understand the inheritance pattern and the risk of passing the condition on to their children.
Early Diagnosis and Treatment: Early diagnosis and treatment are crucial to prevent or delay the progression of organ damage. Regular monitoring and management of symptoms are essential.
Family Screening: Relatives of individuals with Fabry disease should be screened for the condition, particularly if they are experiencing any related symptoms.
Lifestyle Modifications: Following a healthy lifestyle, including a balanced diet, regular exercise, and avoiding smoking, can help manage symptoms and reduce the risk of complications.
Inform healthcare providers: Inform your healthcare providers about your Fabry disease diagnosis to ensure appropriate monitoring, management, and consideration of potential complications.
How long does an outbreak last?
Fabry disease is not an infectious disease and does not have "outbreaks." It is a chronic, progressive condition that persists throughout a person's life. Symptoms can fluctuate in severity, but the underlying genetic defect is always present. Pain crises can be triggered by various external factors, which may be confused with an outbreak, but is not an outbreak of a disease.
How is it diagnosed?
Fabry disease is diagnosed through a combination of clinical evaluation and laboratory testing:
Enzyme Assay: A blood test to measure the activity of the α-Gal A enzyme in leukocytes (white blood cells) or plasma. Significantly reduced or absent α-Gal A activity is indicative of Fabry disease in males.
Genetic Testing: DNA analysis to identify mutations in the GLA gene. This can confirm the diagnosis in both males and females.
Urine Test: Measurement of Gb3 levels in the urine. Elevated levels can suggest Fabry disease.
Kidney Biopsy: In some cases, a kidney biopsy may be performed to examine kidney tissue for Gb3 deposits.
Other Tests: Additional tests may be conducted to assess the extent of organ involvement, such as echocardiography for heart function, nerve conduction studies for nerve damage, and eye exams for corneal opacities.
Timeline of Symptoms
The onset and progression of Fabry disease symptoms can vary, but a general timeline includes:
Childhood/Adolescence: Pain in the hands and feet (acroparasthesia), angiokeratomas, decreased sweating, gastrointestinal problems.
Adulthood: Kidney problems (proteinuria, declining kidney function), heart problems (cardiomyopathy, arrhythmias), neurological problems (stroke, TIA).
Later Life: End-stage renal disease, severe heart failure, increased risk of stroke and death. It's important to note that some individuals may experience symptoms earlier or later than this general timeline.
Important Considerations
Early Diagnosis: Early diagnosis is crucial to initiate treatment and prevent or delay organ damage.
Variable Expression: The severity of Fabry disease can vary significantly, even among family members with the same mutation.
Carrier Status: Females who carry one copy of the mutated GLA gene may or may not experience symptoms. They should be monitored for signs of the disease and receive appropriate treatment if needed.
Multidisciplinary Care: Management of Fabry disease requires a multidisciplinary approach involving specialists such as nephrologists, cardiologists, neurologists, geneticists, and pain management specialists.
Psychological Support: Living with a chronic condition like Fabry disease can be challenging. Psychological support and counseling can help individuals cope with the physical and emotional aspects of the disease.
Research and Clinical Trials: Ongoing research is aimed at developing new and improved therapies for Fabry disease. Individuals may consider participating in clinical trials to contribute to advancements in treatment.