What is the recommended treatment for a 17-year-old female patient with Fabry disease?

Treatment of Fabry Disease in a 17-Year-Old Female

Enzyme replacement therapy (ERT) with agalsidase beta at 1 mg/kg intravenously every 2 weeks is the recommended treatment for this symptomatic 17-year-old female patient with Fabry disease, combined with adjunctive therapies targeting specific symptoms and organ protection. 1, 2

Primary Treatment: Enzyme Replacement Therapy

ERT should be initiated in this female patient if she demonstrates any significant symptoms or progressive organ involvement, including chronic acroparesthesias resistant to conventional therapy, persistent proteinuria (>300 mg/24 hours), GFR below 80 mL/minute/1.73 m², clinically significant cardiac involvement, cerebrovascular events, or chronic disabling gastrointestinal dysfunction. 1

Key Evidence Supporting ERT in Females

• Symptomatic heterozygous females require the same aggressive ERT approach as males, as affected females may display all classical symptoms and face increased risk of hypertrophic cardiomyopathy and cerebrovascular accidents, particularly after age 40. 1, 3

• Women treated with ERT demonstrate reduced left ventricular hypertrophy and reduced plasma and urinary GL-3 levels. 1, 3

• ERT reduces the composite risk of major renal, cardiac, cerebrovascular events, or death by 61% when initiated at earlier stages of disease. 1, 4

Administration Protocol

• Agalsidase beta (Fabrazyme) at 1 mg/kg body weight every 2 weeks via intravenous infusion is the FDA-approved dosing regimen. 1, 2

• Administration must be supervised by a healthcare provider knowledgeable in managing hypersensitivity reactions including anaphylaxis, with immediate access to cardiopulmonary resuscitation equipment. 2

• Premedication with acetaminophen and antihistamines is standard practice to reduce infusion-associated reactions, which occur in approximately 57-59% of patients. 3, 2

• Oral steroids may be added for patients experiencing severe or recurrent infusion-associated reactions. 2

Adjunctive Therapies

Cardiovascular Protection

• Aspirin for reduction of thromboembolic risk factors should be initiated. 1

• Statins for dyslipidemia management to reduce cardiovascular risk. 1, 4

• Strict blood pressure control is essential to minimize ongoing cerebrovascular disease. 4

Renal Protection

• ACE inhibitors or angiotensin-receptor blockers (ARBs) should be prescribed if proteinuria exceeds 300 mg/24 hours or if hypertension develops. 1, 4

• These agents help stabilize renal function, particularly when ERT is initiated before urinary protein excretion reaches 1 g/24 hours. 1

Pain Management

• For neuropathic pain (acroparesthesias), use carbamazepine, gabapentin, or phenytoin as first-line agents. 1, 4, 3

• Avoid NSAIDs due to potential adverse effects on renal function. 4

• Minimize narcotic analgesics to prevent dependency given the chronic nature of Fabry disease. 4

Critical Monitoring Requirements

Baseline Assessment Before Treatment

• Comprehensive evaluation including plasma GL-3 or lyso-Gb3 levels, renal function (serum creatinine, eGFR, 24-hour urine protein or spot urine protein-to-creatinine ratio), and quantified neuropathic pain assessment. 3

• Echocardiography to assess left ventricular mass index and cardiac function. 3

• Brain MRI with T1, T2, and FLAIR-weighted sequences if any neurological symptoms are present. 4

Ongoing Monitoring

• Symptomatic females should be monitored every 6 months (compared to annual monitoring for asymptomatic women). 1

• Annual evaluations must include cardiac monitoring (echocardiography and electrocardiography at least every 2 years) and renal monitoring (urinary protein, creatinine clearance, and creatinine-to-albumin ratio). 4

• Serial plasma GL-3 and lyso-Gb3 measurements to assess treatment response. 3

Important Clinical Caveats

Treatment Timing

• Proteinuria may be reversible if treatment is started early, but lost renal function is not recovered, emphasizing the importance of early initiation. 1

• Treatment benefits on estimated GFR and serum creatinine are more pronounced when therapy begins at less advanced stages of renal dysfunction. 1, 3

Medications to Avoid

• Avoid medications that inhibit α-galactosidase A activity: chloroquine, amiodarone, benoquin, or gentamicin. 4

Limitations of ERT

• ERT cannot completely mitigate valvular disease, acroparesthesias, and risk for cerebrovascular accidents, necessitating aggressive adjunctive antiplatelet therapy and symptom management. 1, 4

• Strokes continue to occur despite ERT, though at reduced rates. 4

Antibody Formation

• Higher anti-agalsidase beta antibody titers are associated with less robust GL-3 clearance, though this does not typically preclude continued treatment. 3

• Patients who test positive for anti-Fabrazyme IgE may be rechallenged with appropriate precautions. 2

Alternative Therapy Consideration

• Migalastat (oral pharmacological chaperone) is an alternative for patients with "amenable" GLA mutations, but requires genetic testing to confirm mutation amenability. 5

• This option is typically considered after establishing the specific mutation profile and may be used as first-line therapy or after switching from ERT. 5