Treatment of Fabry disease
- Michael Mauer, MD
Michael Mauer, MD
- Professor of Pediatrics and Medicine
- University of Minnesota Medical School
- Jeffrey B Kopp, MD
Jeffrey B Kopp, MD
- Senior Investigator, NIDDK, NIH
- Adjunct Professor of Medicine, Uniformed Services University of the Health Sciences
- Section Editors
- Gary C Curhan, MD, ScD
Gary C Curhan, MD, ScD
- Section Editor — Chronic Kidney Disease
- Professor of Medicine
- Harvard Medical School
- Barbara Murphy, MB, BAO, BCh, FRCPI
Barbara Murphy, MB, BAO, BCh, FRCPI
- Section Editor — Renal Transplantation
- Professor of Medicine
- Mount Sinai School of Medicine
Fabry disease, also called Anderson-Fabry disease, is the second most prevalent lysosomal storage disorder after Gaucher's disease. It is an X-linked inborn error of the glycosphingolipid metabolic pathway. This results in accumulation of globotriaosylceramide (Gb3) within lysosomes in a wide variety of cells, thereby leading to the protean manifestations of the disease [1,2].
There is no cure for Fabry disease. Recombinant alpha-galactosidase A (alpha-Gal A), the enzyme that is deficient in patients with Fabry disease, and migalastat hydrochloride, an oral pharmacological chaperone that facilitates trafficking of alpha-Gal A to lysosomes, are therapeutic options for eligible individuals. The impact of these therapies on mortality is unknown.
The treatment and prognosis of Fabry disease is presented here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of this disorder are discussed separately. (See "Clinical features and diagnosis of Fabry disease" and "Clinical features, diagnosis, and management of patients with Fabry disease with cardiac disease" and "Neurologic manifestations of Fabry disease".)
GENERAL APPROACH TO THERAPY
The treatment of patients with Fabry disease primarily focuses upon replacing the missing or deficient enzyme (alpha-galactosidase A, or alpha-Gal A). All classically affected males (ie, with very low or undetectable levels of alpha-Gal A) should receive enzyme replacement therapy (ERT) as soon as the diagnosis is made, regardless of whether or not clinical manifestations are present. Female carriers and atypically affected males (ie, with marginal levels of alpha-Gal A) should receive ERT if clinical manifestations (eg, renal, neurologic, cardiovascular) are present. We also treat patients who have end-stage renal disease (ESRD) with enzyme replacement, as this may reduce cardiovascular and neurologic complications of Fabry disease. Although new approaches are being developed, their role in the treatment of Fabry disease is much less well defined. (See 'Alternatives to ERT' below.)
Patients who develop chronic kidney disease should receive the same monitoring and care as a patient with chronic kidney disease due to a different etiology. (See "Overview of the management of chronic kidney disease in adults".)
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- GENERAL APPROACH TO THERAPY
- USE OF ERT
- Whom to treat with ERT and when to begin
- - Classically affected males
- - Females and males with atypical disease
- - Patients requiring renal replacement therapy
- Dosing of ERT
- - Prevention and treatment of infusion reactions
- - Home therapy
- Monitoring during therapy
- Discontinuation of ERT
- Adverse events
- - Infusion reactions
- - Seroconversion
- Efficacy studies
- - NIH trial
- - International Fabry Disease Study
- - Fabry Disease Clinical Trial Study Group
- - Studies in children
- - Studies in patients with end-stage renal disease
- Alternatives to ERT
- OTHER THERAPIES FOR RENAL DISEASE
- Antihypertensive therapy with a RAS inhibitor
- - Recurrence of Fabry disease
- OTHER THERAPIES FOR PAIN
- Other long-term outcomes
- SUMMARY AND RECOMMENDATIONS