What are the management options for Fabry disease?

Management of Fabry Disease

Enzyme replacement therapy (ERT) is strongly recommended as the primary treatment for all patients with Fabry disease to address the underlying pathophysiology and prevent disease progression. 1

Diagnosis and Initial Assessment

• Diagnosis is confirmed by determining α-galactosidase A activity in plasma or peripheral leukocytes in males
• For female carriers, genetic testing to identify specific mutations in the α-galactosidase A gene is necessary as enzyme activity may be normal to very low 2
• Comprehensive baseline evaluation of multiple organ systems is essential:
  • Renal: GFR, proteinuria, albuminuria
  • Cardiac: Echocardiography, ECG, cardiac biomarkers
  • Neurologic: Brain MRI, pain assessment
  • Ophthalmologic: Slit-lamp examination
  • Dermatologic: Assessment for angiokeratomas
  • Auditory: Audiometry

Treatment Options

1. Enzyme Replacement Therapy (First-Line)

• Agalsidase beta (Fabrazyme): 1 mg/kg IV every 2 weeks 1, 3

  • Demonstrated efficacy in clearing globotriaosylceramide (GL-3) from vascular endothelium
  • Shown to slow decline in renal function, particularly in patients with Stage III chronic kidney disease 4
  • May reduce neuropathic pain, though improvement can be gradual

• Agalsidase alfa: 0.2 mg/kg IV every 2 weeks 4, 5

  • Demonstrated safety in long-term use
  • Helps maintain organ function and reduces GL-3 levels

2. Oral Chaperone Therapy

• Migalastat: 123 mg orally every other day 6, 7
  • Only for patients with amenable GLA gene variants
  • Take on empty stomach (4-hour fast around dosing)
  • Consultation with clinical genetics professional recommended for variant interpretation

3. Supportive and Symptomatic Management

• Pain management:

  • Anticonvulsants (phenytoin, carbamazepine, gabapentin) for neuropathic pain 2
  • Avoid narcotic analgesics due to risk of dependency 2

• Renal protection:

  • ACE inhibitors or ARBs for proteinuria
  • Goal is to minimize proteinuria regardless of blood pressure 2

• Cardiovascular management:

  • Control of cardiac risk factors
  • Consider cardiac pacing for conduction abnormalities 2

• Cerebrovascular protection:

  • Antiplatelet therapy (aspirin, clopidogrel) to reduce stroke risk 2
  • Maintain adequate hydration

• Gastrointestinal symptoms:

  • Pancrelipase or metoclopramide for GI symptoms 2

Monitoring and Follow-up

Regular monitoring is essential to assess treatment response:

• Renal function: GFR, proteinuria every 3-6 months
• Cardiac: Echocardiography, ECG every 1-2 years
• Neurologic: Brain MRI every 2 years or if symptoms occur
• Biomarkers: Plasma GL-3 and Lyso-GL-3 levels
• Monitor for antibody formation to ERT 1, 3

Special Considerations

• Early treatment: Initiate ERT as soon as clinical signs appear, even in children, to prevent irreversible organ damage 2
• Female carriers: Treat symptomatic females with ERT 2
• Dialysis patients: Continue ERT as it may reduce cardiac and cerebrovascular complications 2
• Infusion reactions: Pre-medicate with antihistamines, antipyretics, or corticosteroids if reactions occur 3
• Pregnancy: Limited data on ERT use during pregnancy; report exposure to registry 3

Pitfalls to Avoid

• Delaying diagnosis due to nonspecific symptoms that mimic other conditions
• Failing to recognize disease in female carriers who can have significant manifestations
• Inadequate monitoring of multi-organ involvement
• Not adjusting ERT dosing when clinical response is suboptimal
• Overlooking the need for patient education and genetic counseling

ERT has transformed the management of Fabry disease from purely symptomatic to disease-modifying therapy. While it may not reverse all established organ damage, it can significantly slow disease progression and improve quality of life when started early.