Summary about Disease
Deficiency of alpha-galactosidase A refers to Fabry disease, a rare, inherited lysosomal storage disorder. It is caused by a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A), which leads to the accumulation of a fatty substance called globotriaosylceramide (Gb3) or GL-3 within cells throughout the body. This build-up can damage various organs and tissues, leading to a range of symptoms.
Symptoms
Symptoms of Fabry disease are highly variable, both in severity and the organs affected. Common symptoms include:
Angiokeratomas (small, dark red spots on the skin)
Burning pain in hands and feet (acroparesthesia)
Decreased sweating (hypohidrosis)
Gastrointestinal problems (abdominal pain, diarrhea, nausea)
Clouding of the cornea (corneal verticillata)
Kidney disease
Heart problems (cardiomyopathy, arrhythmias)
Stroke
Tinnitus 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 result in a deficiency or complete absence of functional alpha-Gal A. The disease is inherited in an X-linked pattern. Males, having only one X chromosome, are typically more severely affected. Females, with two X chromosomes, can be affected to varying degrees due to X-inactivation.
Medicine Used
The primary treatments for Fabry disease include:
Enzyme Replacement Therapy (ERT): Involves intravenous infusions of a functional alpha-Gal A enzyme. Two ERT drugs are available: agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme).
Chaperone Therapy: Migalastat (Galafold) is a chaperone therapy that stabilizes the body's own mutated alpha-Gal A enzyme, enhancing its activity. It is only effective for specific GLA gene mutations.
Supportive therapies to treat specific symptoms such as pain medications for chronic pain, GI medications, and cardiac medications
Is Communicable
Fabry disease is not communicable. It is a genetic disorder passed down through families, not an infectious disease spread from person to person.
Precautions
There are no specific precautions to prevent contracting Fabry disease, as it is a genetic condition. For individuals with Fabry disease, precautions focus on managing symptoms and preventing complications:
Regular monitoring by specialists (nephrologist, cardiologist, neurologist)
Adherence to prescribed medications (ERT, chaperone therapy, pain management)
Lifestyle modifications (diet, exercise) as recommended by physicians.
Genetic counseling for affected individuals and families to understand the inheritance pattern and risks of passing the gene to offspring.
How long does an outbreak last?
Fabry disease is not an infectious disease and therefore does not have outbreaks. It is a chronic condition that lasts a lifetime. Symptom severity can fluctuate over time, but the underlying genetic defect remains constant.
How is it diagnosed?
Fabry disease is diagnosed through a combination of clinical evaluation and laboratory testing:
Enzyme Assay: Measures the activity level of alpha-Gal A enzyme in blood (leukocytes) or skin fibroblasts. Reduced or absent enzyme activity indicates Fabry disease.
Genetic Testing: GLA gene sequencing to identify mutations confirms the diagnosis and helps with genetic counseling.
Urine Test: Analysis of urine to measure the amount of globotriaosylceramide (GL-3).
Tissue Biopsy: In some cases, a kidney biopsy may be performed to assess GL-3 accumulation in kidney cells.
Cardiac Evaluation: Echocardiogram and MRI to assess heart function.
Timeline of Symptoms
The timeline of Fabry disease symptoms varies considerably. Some individuals experience symptoms in childhood or adolescence, while others may not develop noticeable symptoms until adulthood.
Childhood/Adolescence: Often marked by acroparesthesia (pain in hands and feet), gastrointestinal problems, angiokeratomas, and corneal verticillata.
Adulthood: Kidney disease, heart problems (cardiomyopathy, arrhythmias), and stroke become more prominent.
The rate of disease progression also varies among individuals. Early diagnosis and treatment can help slow disease progression and manage complications.
Important Considerations
Fabry disease is often underdiagnosed due to its variable presentation and rarity.
Early diagnosis and treatment are crucial to prevent or delay organ damage.
Genetic counseling is essential for affected individuals and families.
Individuals with Fabry disease require comprehensive, multidisciplinary care from specialists.
New therapies and research are continually emerging, offering hope for improved treatment outcomes.