Fabry Disease
Disease Details
Family Health Simplified
- Description
- Fabry disease is a genetic disorder resulting from the buildup of a specific type of fat, due to a deficiency in the enzyme alpha-galactosidase A, leading to a range of systemic symptoms including pain, kidney failure, heart issues, and strokes.
- Type
- Fabry disease is an X-linked recessive disorder. This means that the defective gene responsible for the disease is located on the X chromosome, and males (who have only one X chromosome) are more severely affected, while females (who have two X chromosomes) can be carriers and may exhibit mild to severe symptoms.
- Signs And Symptoms
- Symptoms are typically first experienced in early childhood and can be very difficult to diagnose; the rarity of Fabry disease to many clinicians sometimes leads to misdiagnoses. Manifestations of the disease usually increase in number and severity as an individual ages.
- Prognosis
- Life expectancy with Fabry disease for males was 58.2 years, compared with 74.7 years in the general population, and for females 75.4 years compared with 80.0 years in the general population, according to registry data from 2001 to 2008. The most common cause of death was cardiovascular disease, and most of those had received kidney replacements.
- Onset
- Fabry disease typically has an onset in childhood or adolescence, although the severity and specific symptoms can vary widely between individuals. In males, early signs may include episodes of pain, particularly in the hands and feet (acroparesthesias), and gastrointestinal symptoms. As the disease progresses, complications can involve the kidneys, heart, and brain. Women, due to their heterozygous status, may experience milder forms of the disease and have a later onset of symptoms.
- Prevalence
- Fabry disease is a rare genetic disorder. Its prevalence is approximately 1 in 40,000 to 1 in 117,000 males. It is less common in females but can still occur.
- Epidemiology
- Fabry disease is panethnic, but due to its rarity, determining an accurate disease frequency is difficult. Reported incidences, ranging from one in 476,000 to one in 117,000 in the general population, may largely underestimate the true prevalence. Newborn screening initiatives have found an unexpectedly high prevalence of the disease, as high as one in about 3,100 newborns in Italy and have identified a surprisingly high frequency of newborn males around one in 1,500 in Taiwan.
- Intractability
- Fabry disease is considered intractable in the sense that it is a chronic genetic condition with no cure. However, treatments such as enzyme replacement therapy (ERT) and chaperone therapy can help manage symptoms and slow disease progression. Early diagnosis and consistent treatment are crucial for improving quality of life and outcomes for individuals with Fabry disease.
- Disease Severity
- Fabry disease is a rare genetic disorder that can vary in severity among affected individuals. The severity depends largely on the type of mutation in the GLA gene and can range from mild to severe. Classic Fabry disease, which typically presents in childhood, is generally more severe and involves multi-organ dysfunction, including renal failure, cardiac complications, and early strokes. The later-onset form is usually milder and may predominantly affect the heart and kidneys. The enzyme replacement therapies and other treatments available can help manage symptoms and improve quality of life.
- Healthcare Professionals
- Disease Ontology ID - DOID:14499
- Pathophysiology
- Fabry disease is a genetic disorder caused by mutations in the GLA gene, which leads to a deficiency or malfunction of the enzyme alpha-galactosidase A. This enzyme deficiency results in the accumulation of globotriaosylceramide (Gb3 or GL-3) in various tissues, including the blood vessels, kidneys, heart, and nervous system. The buildup of Gb3 disrupts cell function and causes the various symptoms and complications associated with Fabry disease, including pain, kidney failure, heart problems, and stroke.
- Carrier Status
- Fabry disease is a genetic disorder related to the X chromosome. Carrier status typically affects females, as they have two X chromosomes, while males have only one. Female carriers usually have one mutated GLA gene and one normal GLA gene. They may or may not exhibit symptoms, depending on the level of enzyme deficiency. Males, having only one X chromosome, are more likely to display full-blown symptoms if they inherit the mutated gene. "Nan" appears to be a typographical error and doesn't relate to Fabry disease in this context.
- Mechanism
- Fabry disease is an inherited lysosomal storage disorder that is caused by a deficiency of alpha-galactosidase A. This enzyme deficiency is a result of an accumulation of glycosphingolipids found in the lysosomes and most cell types and tissues, which leads it to be considered a multisystem disease. Indications include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. In severe cases there is renal, cerebrovascular, and cardiac involvement and it is predominately responsible for premature mortality in Fabry patients. Fabry disease is X-linked and manifests mostly in homozygous males but also in heterozygous females. Cardiac involvement is recurrent in Fabry patients. Patients have developed hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Deficient activity of lysosomal alpha-galactosidase results in progressive accumulation of globotriaosylceramide (GL-3) within lysosomes, that is believed to trigger a cascade of cellular events. The demonstration of marked alpha-galactosidase deficiency is the conclusive method for the diagnosis in homozygous males. It may be detected in heterozygotous females, but it is often inconclusive due to random X-chromosomal inactivation, so molecular testing (genotyping) of females is mandatory.
- Treatment
- The treatments available for Fabry disease can be divided into therapies that aim to correct the underlying problem of decreased activity of the alpha galactosidase A enzyme and thereby reduce the risk of organ damage, and therapies to improve symptoms and life expectancy once organ damage has already occurred.
- Compassionate Use Treatment
-
For Fabry disease, compassionate use treatment and off-label or experimental treatments may include:
1. **Compassionate Use Treatment**:
- **Enzyme Replacement Therapy (ERT)**:
- Agalsidase alfa (Replagal)
- Agalsidase beta (Fabrazyme)
These are the standard treatments but may be provided under compassionate use in countries where they are not yet approved or available.
2. **Off-Label or Experimental Treatments**:
- **Chaperone Therapy**:
- Migalastat (Galafold): This is approved for certain mutations but might be used off-label for others.
- **Substrate Reduction Therapy (SRT)**:
- Eliglustat: Primarily approved for Gaucher disease but under investigation for use in Fabry disease.
- **Gene Therapy**:
- Investigational gene therapies are being developed and tested in clinical trials, aiming to introduce functional copies of the GLA gene.
- **Second-generation ERTs**:
- Pegunigalsidase alfa (PRX-102): An experimental agent studied for its prolonged half-life and reduced immunogenicity.
Participation in clinical trials can also provide access to these experimental treatments. - Lifestyle Recommendations
-
Lifestyle recommendations for managing Fabry disease include:
1. **Regular Exercise**: Engage in moderate physical activity to improve overall cardiovascular health, but avoid overexertion.
2. **Balanced Diet**: Follow a healthy diet to manage weight and support heart and kidney health. Limit foods high in sodium and saturated fats.
3. **Hydration**: Stay well-hydrated to support kidney function and reduce the risk of kidney complications.
4. **Avoid Extreme Temperatures**: Extreme heat or cold can worsen symptoms, so dress appropriately for the weather and avoid extreme conditions.
5. **Stress Management**: Practice stress-reducing techniques such as yoga, meditation, or breathing exercises.
6. **Regular Medical Check-Ups**: Keep regular appointments with healthcare providers to monitor and manage symptoms and prevent complications.
7. **Medication Adherence**: Follow prescribed treatments, including enzyme replacement therapy or other medications, as directed by a healthcare provider.
8. **Support Networks**: Seek support from patient groups or counseling to manage the emotional and psychological impacts of the disease. - Medication
- For Fabry disease, medication primarily involves enzyme replacement therapy (ERT) to reduce symptoms and slow disease progression. Common ERT options include agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). Another treatment option is the oral chaperone therapy migalastat (Galafold), which is suitable for patients with amenable genetic mutations. Pain management, kidney protection, and cardiovascular monitoring are also essential aspects of treating Fabry disease.
- Repurposable Drugs
-
Fabry disease is a genetic lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A. There are some drugs that have been repurposed for the treatment of Fabry disease:
1. Migalastat: Originally developed to stabilize certain enzymes, it acts as a pharmacological chaperone to stabilize dysfunctional alpha-galactosidase A in patients with amenable mutations.
2. Enzyme Replacement Therapies (ERT): Agalsidase alpha (Replagal) and agalsidase beta (Fabrazyme) are forms of recombinant alpha-galactosidase A used to replace the deficient enzyme.
Please consult with a healthcare provider for additional and updated information on treatment options. - Metabolites
- In Fabry disease, there is an accumulation of a specific metabolite called globotriaosylceramide (Gb3 or GL-3) in various tissues of the body. This buildup is due to the deficiency or malfunctioning of the enzyme alpha-galactosidase A, which is responsible for breaking down Gb3. Elevated levels of Gb3 and other related glycosphingolipids lead to the progressive symptoms and complications of Fabry disease.
- Nutraceuticals
- There are no well-established nutraceutical treatments specifically for Fabry disease. Fabry disease is a genetic disorder caused by the build-up of a type of fat, called globotriaosylceramide, due to the deficiency of the enzyme alpha-galactosidase A. The primary treatments include enzyme replacement therapy (ERT) and pharmacological chaperone therapy to manage symptoms and slow disease progression. Nutraceuticals are not a recognized standard of care for this condition. Always consult healthcare professionals for treatment and management options.
- Peptides
- Fabry disease is a genetic disorder resulting from the buildup of a particular type of fat, called globotriaosylceramide, due to a deficiency in the enzyme alpha-galactosidase A. As for peptides, enzyme replacement therapy (ERT) using recombinant alpha-galactosidase A is a standard treatment option aimed at replacing the deficient enzyme. Treatment approaches involving peptides might also include chaperone therapy with small molecules that stabilize the enzyme. There isn’t a direct link to “nan” (nanotechnology) in current standard treatments, but research is ongoing to explore new methods, including nanotechnology-based delivery systems, for enhancing the efficacy and targeting of ERT.