- Article
- Source: Campus Sanofi
- Jun 18, 2025
Fabry Disease Treatment and Management
Fabry Disease Treatment and Management
Fabry disease is caused by a deficiency in α-galactosidase A (α-gal A), which leads to an accumulation of globotriaosylceramide (GL-3) and lyso-GL3 in various tissues, resulting in multiorgan damage.1,2
Established treatment guidelines recommend treatment begin as soon as possible after diagnosis of classic Fabry disease.3
Current treatment approaches consist of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy, and adjunctive supportive therapy.4
Multidisciplinary Approach in Fabry Disease Management
A multidisciplinary approach is key to coordinated care in Fabry disease.5 The care team may include specialists such as geneticists, genetic counselors, nephrologists, neurologists, and cardiologists, among other healthcare professionals.6,7
Every year, patients should be screened for new symptoms, and each of these specialties have a vital role in monitoring symptom progression.7 The Fabry Disease Schedule of Assessments provides more guidance on symptom monitoring.
Fabry Disease Schedule of Assessments
The Fabry Disease Schedule of Assessments was developed by the Fabry Registry Board of Advisors.8
These Schedules of Assessment are intended to serve as guidance, not requirements; treating physicians determine the actual frequency of necessary assessments according to a patient's individualized need for medical care and routine follow-up.8
Individualized Fabry Disease Treatment Planning
It is recommended that all patients with Fabry disease have baseline evaluations and routine monitoring to evaluate organ involvement, and disease progression. For those patients treated with disease-specific therapy, routine monitoring enables assessment of therapeutic response.3
The heterogeneity of clinical features and multi-organ system pathology of Fabry disease necessitate a comprehensive care plan with individualized therapeutic goals.3 For example, females with Fabry may experience a later age of onset of some clinical manifestations.9
Individualized treatment plans should be discussed and agreed upon with the patient and their family after diagnosis.3
Current Fabry Disease Treatments and Medications
Established treatments to reduce GL-3 buildup include ERT, which works by restoring α-GAL levels, and molecular chaperone therapy, which functions by stabilizing misfolded proteins, facilitating proper trafficking of the enzyme to lysosomes for patients with amenable variants.10
| Property | Enzyme Replacement Therapy (ERT) | Molecular Chaperone Therapy |
| Administration | Intravenous infusions, weight based dosing, every two weeks.1,3,4 | Oral administration, taken every other day.1,3,4 |
| Mechanism of action | Provides the body with a functional version of the enzyme, alpha-galactosidase A (alpha-GAL A), that is deficient or dysfunctional in individuals with Fabry disease, working to address the accumulation of Gb3/GL3 in lysosomes.1,3,4 | Stabilizes misfolded but functional α-galactosidase A, promoting its proper folding and trafficking to lysosomes to restore enzyme activity in Fabry disease.11 |
| Number of approved therapies | 2 approved ERTs in the US1,3,4 | 111 |
Enzyme replacement therapy (ERT)
ERT was the first disease-specific treatment for Fabry disease.10 ERT is administered through intravenous infusion and it works by addressing the accumulation of substrate.10
Molecular Chaperone Therapy
Some Fabry disease patients have specific genetic variants of the GLA gene, which result in misfolded α-GAL A.12
These misfolded α-galactosidase A retain their normal catalytic function but with reduced stability, leading to premature destruction by endoplasmic reticulum (ER) associated protein degradation (ERAD).12
Chaperone therapy functions by promoting enzyme folding and stability, allowing trafficking of α-GAL to the lysosome.12 Once the α-Gal A-chaperone complex enters the lysosome, the chaperone is dissociated from the enzyme and α-Gal A is free to act on glycosphingolipid substrates.12
Fabry Disease Treatment Guidelines
According to established treatment guidelines, effective management of Fabry disease in adult patients requires the following13:
- A personalized treatment approach
- Comprehensive evaluation of disease involvement prior to initiation of disease-specific therapy
- Management by an experienced multidisciplinary team
Established guidelines recommend that disease-specific therapy should be considered in the following instances5,14:
Adult patients:
- Adult male patients with classic GLA variant: Disease-specific therapy should be considered and is appropriate whether symptomatic or asymptomatic at any age of presentation
- Symptomatic adult female patients with classic GLA variant: Signs and symptoms suggesting major organ involvement, including proteinuria/albuminuria or cardiac involvement not attributable to other causes, stroke or TIA, neuropathic pain, exercise intolerance and impaired sweating
- Asymptomatic adult female patients with classic GLA variant: Signs and symptoms suggesting major organ involvement, including lab/histological/imaging evidence of injury to kidney, heart, or CNS
- Adult male and female patients with non-classic GLA variant: Signs and symptoms suggesting major organ involvement, including lab/histological/imaging evidence of injury to kidney, heart, or CNS
Pediatric patients:
- Symptomatic pediatric male or female patients: Signs and symptoms suggesting major organ involvement, including neuropathic pain, decline in eGFR, pathological albuminuria/proteinuria, creatinine elevation, cardiomyopathy or arrhythmia, recurrent abdominal pain and diarrhea, exercise intolerance and impaired sweating. Recommendations to initiate treatment apply to patients 2 years of age and older
- Asymptomatic pediatric male patients with classic GLA variant: Signs and symptoms suggesting major organ involvement, including neuropathic pain, decline in eGFR, pathological albuminuria/proteinuria, creatinine elevation, cardiomyopathy or arrhythmia, recurrent abdominal pain and diarrhea, exercise intolerance and impaired sweating. Serious discussion regarding the timing of ERT initiation is recommended by age 8–10 years for asymptomatic boys with classic variants
- Asymptomatic pediatric male or female patients with non-classic GLA variant or variant of unknown significance: Signs and symptoms suggesting major organ involvement, including neuropathic pain, decline in eGFR, pathological albuminuria/proteinuria, creatinine elevation, cardiomyopathy or arrhythmia, recurrent abdominal pain and diarrhea, exercise intolerance and impaired sweating
For the effective Fabry disease management in pediatric patients, the following points should be considered3,15:
- Early diagnosis and longitudinal monitoring
- Early treatment initiation as appropriate
- ERT for all symptomatic children over the age of 2 years, regardless of sex or symptom severity
- Treatment consideration for asymptomatic boys with classic GLA variants from ages 8–10, following comprehensive evaluation and family discussion
- Asymptomatic girls require ongoing monitoring with attention to early signs
- Management should be guided by an experienced multidisciplinary team led by a Fabry disease expert
Symptom Management in Fabry Disease
Palliative therapy for Fabry disease aims to alleviate symptoms and improve quality of life for patients with the disease.4
Several palliative therapies are commonly used for patients with Fabry disease, including4:
- Pain management: Analgesics may help manage neuropathic pain in Fabry disease
- Cardiac care: Medications and devices can help manage heart complications like LVH, arrhythmias, and heart failure
- Reno-protective medication: ACEi, ARBs, diuretics, and low-sodium diet can help manage hypertension and CKD
- Gastrointestinal management: Dietary changes and medications may help manage gastric dysmotility and discomfort
- Auditory impairment: Hearing aids and cochlear implants may help address hearing loss in patients with Fabry disease
- Pulmonary care: Smoking cessation and bronchodilators may support pulmonary health
- Physical therapy: May improve mobility, muscle strength, and aid with pain management
- Occupational therapy: Supports independence in daily activities
- Psychological support: Counseling and therapy can address emotional and mental health needs
Early Treatment Initiation Is Crucial in Fabry Disease Management
Early diagnosis and prompt treatment initiation are crucial for slowing disease progression and the prevention of irreversible organ damage.5
- Mesangial cells: Cells in the glomerulus of the kidney, playing a crucial role in glomerular filtration and kidney function16
- Podocytes: Epithelial cells playing a vital role in kidney function, specifically in the glomerular filtration process17
- Tubular epithelial cells: Cells lining the tubules of various organs, including the kidneys, and playing crucial roles in reabsorption, secretion, and maintaining fluid and electrolyte balance18
- Endoplasmic Reticulum-Associated Degradation (ERAD): Cellular process where misfolded or damaged proteins are identified in the endoplasmic reticulum (ER) and then transported out of the ER to the cytoplasm for degradation by the proteasome19
- Variant: Changes in the DNA sequence of the GLA gene, which may or may not be pathogenic. Fabry disease patients can be classified with a classic GLA variant or a non-classic GLA variant20
- Amenable variants: Genetic change in the GLA gene that produces a misfolded but potentially functional α-Gal A enzyme, which can be stabilized by pharmacological chaperone therapy1,3,4
- Glucosylceramide synthase (GCS): An enzyme crucial for the synthesis of various glycosphingolipids, including Gb39
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