Summary about Disease
Fabry disease is a rare, inherited (genetic) disorder that results from the buildup of a specific type of fat, called globotriaosylceramide (Gb3), in the body's cells. This buildup occurs because individuals with Fabry disease have a deficiency or complete absence of the enzyme alpha-galactosidase A (alpha-Gal A), which is needed to break down Gb3. The accumulation of Gb3 can damage various organs and tissues, including the kidneys, heart, brain, and skin. It is a type of lysosomal storage disorder.
Symptoms
Symptoms of Fabry disease vary widely among individuals, even within the same family. Some common symptoms include:
Angiokeratomas (small, dark red spots on the skin, especially in the "bathing trunk" area)
Acroesthesia (burning pain in the hands and feet)
Decreased sweating (hypohidrosis) or absence of sweating (anhidrosis)
Corneal opacities (clouding of the cornea, which usually doesn't affect vision)
Gastrointestinal problems (abdominal pain, diarrhea, nausea)
Kidney problems (proteinuria, kidney failure)
Heart problems (cardiomyopathy, arrhythmias, heart valve abnormalities)
Stroke
Tinnitus (ringing in the ears) and hearing loss
Fatigue
Depression
Causes
Fabry disease is caused by mutations in the GLA gene, which provides instructions for making the alpha-Gal A enzyme. These mutations lead to a deficiency or absence of the enzyme, resulting in the buildup of Gb3. Fabry disease is inherited in an X-linked manner. Males, having only one X chromosome, will express the disease if they inherit the mutated gene. Females, having two X chromosomes, may express the disease to varying degrees, depending on the pattern of X-chromosome inactivation.
Medicine Used
Treatment for Fabry disease focuses on managing symptoms and preventing organ damage. Available treatment options include:
Enzyme replacement therapy (ERT): ERT involves intravenous infusions of a synthetic version of the alpha-Gal A enzyme. Examples include agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme).
Chaperone therapy: Migalastat (Galafold) is a chaperone therapy that works by stabilizing the body's own alpha-Gal A enzyme, allowing it to function better. It is only effective for individuals with specific GLA mutations that are amenable to chaperone therapy.
Symptomatic treatment: Medications can be used to manage specific symptoms, such as pain medications for acroesthesia, ACE inhibitors or ARBs for kidney problems, and medications for heart problems.
Is Communicable
No, Fabry disease is not communicable. It is a genetic disorder that is inherited from parents to offspring. It cannot be spread from person to person through contact, air, or any other means.
Precautions
Since Fabry disease is genetic, there are no precautions to prevent acquiring the disease. However, for individuals with Fabry disease, the following precautions are important:
Adherence to treatment: Following prescribed medications and therapies is crucial for managing the disease and preventing complications.
Regular monitoring: Regular checkups with a physician, including monitoring of kidney, heart, and neurological function, are essential.
Lifestyle modifications: Maintaining a healthy lifestyle, including a balanced diet, regular exercise, and avoiding smoking, can help to support overall health and well-being.
Genetic counseling: Genetic counseling can help individuals with Fabry disease and their families understand the inheritance pattern of the disease and assess the risk of passing it on to future generations.
Avoidance of certain medications: Certain medications, such as some NSAIDs, can worsen kidney function and should be used with caution.
How long does an outbreak last?
Fabry disease is not an outbreak-related illness. It is a chronic, progressive condition. Symptoms can appear in childhood and worsen over time. There is no "outbreak" of Fabry disease that resolves within a specific timeframe. It is a lifelong condition requiring ongoing management.
How is it diagnosed?
Fabry disease can be diagnosed through the following methods:
Enzyme assay: A blood test to measure the level of alpha-Gal A enzyme activity. This is the primary diagnostic test for males.
Genetic testing: Analysis of the GLA gene to identify mutations. This is important for confirming the diagnosis, especially in females, and for family screening.
Urine test: To measure the level of Gb3 in the urine.
Kidney biopsy: In some cases, a kidney biopsy may be performed to examine kidney tissue for the presence of Gb3 deposits.
Cardiac evaluation: An ECG, echocardiogram, or MRI to look for heart involvement.
Skin biopsy: To detect angiokeratomas
Timeline of Symptoms
The timeline of symptoms in Fabry disease varies greatly. However, a general pattern can be observed:
Childhood/Adolescence: Pain in the hands and feet (acroesthesia), angiokeratomas, decreased sweating, gastrointestinal problems.
Adulthood: Kidney problems, heart problems, stroke, hearing loss, corneal opacities, fatigue, depression.
Later Life: Progressive kidney and heart failure, increased risk of stroke and other complications. It is important to note that some individuals may experience severe symptoms early in life, while others may have mild symptoms that only become noticeable in adulthood.
Important Considerations
Early diagnosis is crucial: Early diagnosis and treatment can help to prevent or delay the onset of serious complications.
Genetic counseling is important for families: Fabry disease is inherited, so genetic counseling can help families understand the risks and make informed decisions about family planning.
Treatment is lifelong: Treatment for Fabry disease is typically lifelong and requires ongoing monitoring and management.
Disease heterogeneity: Fabry disease can present with a wide range of symptoms and severity, making diagnosis and management challenging.
Increased risk of cardiovascular events: Individuals with Fabry disease are at increased risk of heart attacks and strokes.
Psychological impact: The chronic nature of Fabry disease and its associated symptoms can have a significant impact on mental health and well-being. Support groups and counseling can be helpful.
Multidisciplinary care: Managing Fabry disease often requires a team of specialists, including nephrologists, cardiologists, neurologists, and geneticists.