This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (446)  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in JAMA  Topic Collections  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Raphael Schiffmann, MD; Jeffrey B. Kopp, MD; Howard A. Austin III, MD; Sharda Sabnis, MD; David F. Moore, MD, PhD; Thais Weibel, MD; James E. Balow, MD; Roscoe O. Brady, MD

JAMA. 2001;285:2743-2749.

Context  Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme -galactosidase A (-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease.

Objective  To evaluate the safety and efficacy of intravenous -gal A for Fabry disease.

Design and Setting  Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health.

Patients  Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by -gal A assay.

Intervention  A dosage of 0.2 mg/kg of -gal A, administered intravenously every other week (12 doses total).

Main Outcome Measure  Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI).

Results  Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with -gal A vs no significant change in the placebo group (P = .02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving -gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P = .05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving -gal vs a 16.5% increase for placebo (P = .01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving -gal A vs 19.5 mL/min for placebo (P = .19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving -gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P = .02). In patients treated with -gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight.

Conclusion  Intravenous infusions of -gal A are safe and have widespread therapeutic efficacy in Fabry disease.

Author Affiliations: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke (Drs Schiffmann, Moore, Weibel, and Brady), and Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases (Drs Kopp, Austin, and Balow), National Institutes of Health, Bethesda, Md; Division of Nephropathology, Armed Forces Institute of Pathology, Washington, DC (Dr Sabnis).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTER

Skin Manifestations of Fabry Disease
Matthias Möhrenschlager, Johannes Ring, Dietrich Abeck, and Raphael Schiffmann
JAMA. 2001;286(11):1315.
EXTRACT | FULL TEXT  

RELATED ARTICLE

June 6, 2001
JAMA. 2001;285(21):2793-2794.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Catalytic Mechanism of Human {alpha}-Galactosidase
Guce et al.
J. Biol. Chem. 2010;285:3625-3632.
ABSTRACT | FULL TEXT  

End-stage renal disease in patients with Fabry disease: natural history data from the Fabry Registry
Ortiz et al.
Nephrol Dial Transplant 2009;0:gfp554v1-gfp554.
ABSTRACT | FULL TEXT  

Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey
Mehta et al.
J. Med. Genet. 2009;46:548-552.
ABSTRACT | FULL TEXT  

Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy
Schiffmann et al.
Nephrol Dial Transplant 2009;24:2102-2111.
ABSTRACT | FULL TEXT  

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study
Imbriaco et al.
Heart 2009;95:1103-1107.
ABSTRACT | FULL TEXT  

Nephropathy in Fabry disease: the importance of early diagnosis and testing in high-risk populations
Oqvist et al.
Nephrol Dial Transplant 2009;24:1736-1743.
FULL TEXT  

Agalsidase Alfa and Kidney Dysfunction in Fabry Disease
West et al.
J. Am. Soc. Nephrol. 2009;20:1132-1139.
ABSTRACT | FULL TEXT  

Genetics of Atherothrombotic and Lacunar Stroke
Debette and Seshadri
Circ Cardiovasc Genet 2009;2:191-198.
FULL TEXT  

Preclinical Efficacy and Safety of 1-Deoxygalactonojirimycin in Mice for Fabry Disease
Ishii et al.
J. Pharmacol. Exp. Ther. 2009;328:723-731.
ABSTRACT | FULL TEXT  

Stroke in Fabry Disease Frequently Occurs Before Diagnosis and in the Absence of Other Clinical Events: Natural History Data From the Fabry Registry
Sims et al.
Stroke 2009;40:788-794.
ABSTRACT | FULL TEXT  

Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy: Evidence for a Better Outcome With Early Treatment
Weidemann et al.
Circulation 2009;119:524-529.
ABSTRACT | FULL TEXT  

Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients
Schoenmakere et al.
Nephrol Dial Transplant 2008;23:4044-4048.
ABSTRACT | FULL TEXT  

Central nervous system involvement in Anderson-Fabry disease: a clinical and MRI retrospective study
Buechner et al.
J. Neurol. Neurosurg. Psychiatry 2008;79:1249-1254.
ABSTRACT | FULL TEXT  

Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy
Kovacevic-Preradovic et al.
Eur J Echocardiogr 2008;9:729-735.
ABSTRACT | FULL TEXT  

The Binary Endocardial Appearance Is a Poor Discriminator of Anderson-Fabry Disease From Familial Hypertrophic Cardiomyopathy
Kounas et al.
J Am Coll Cardiol 2008;51:2058-2061.
ABSTRACT | FULL TEXT  

Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy
Ortiz et al.
Nephrol Dial Transplant 2008;23:1600-1607.
ABSTRACT | FULL TEXT  

Elevated globotriaosylsphingosine is a hallmark of Fabry disease
Aerts et al.
Proc. Natl. Acad. Sci. USA 2008;105:2812-2817.
ABSTRACT | FULL TEXT  

Treatment of Anderson Fabry disease
Linhart
Heart 2008;94:138-139.
FULL TEXT  

Fabry nephropathy: 5 years of enzyme replacement therapy--a short review
Barbey et al.
NDT Plus 2008;1:11-19.
FULL TEXT  

Effects of enzyme replacement therapy on the cardiomyopathy of Anderson Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa
Hughes et al.
Heart 2008;94:153-158.
ABSTRACT | FULL TEXT  

Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population
Terryn et al.
Nephrol Dial Transplant 2008;23:294-300.
ABSTRACT | FULL TEXT  

Screening for Fabry Disease in Patients with Chronic Kidney Disease: Limitations of Plasma {alpha}-Galactosidase Assay as a Screening Test
Andrade et al.
CJASN 2008;3:139-145.
ABSTRACT | FULL TEXT  

Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents
Ries et al.
J Clin Pharmacol 2007;47:1222-1230.
ABSTRACT | FULL TEXT  

Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease
Pastores et al.
Nephrol Dial Transplant 2007;22:1920-1925.
ABSTRACT | FULL TEXT  

Elevated Endothelial Microparticles in Fabry Children Decreased After Enzyme Replacement Therapy
Gelderman et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:e138-e139.
FULL TEXT  

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach
Moore et al.
Proc. Natl. Acad. Sci. USA 2007;104:8065-8070.
ABSTRACT | FULL TEXT  

Weekly Enzyme Replacement Therapy May Slow Decline of Renal Function in Patients with Fabry Disease Who Are on Long-Term Biweekly Dosing
Schiffmann et al.
J. Am. Soc. Nephrol. 2007;18:1576-1583.
ABSTRACT | FULL TEXT  

Enzyme Replacement Therapy and Fabry Kidney Disease: Quo Vadis?
Warnock
J. Am. Soc. Nephrol. 2007;18:1368-1370.
FULL TEXT  

The heart in Anderson-Fabry disease and other lysosomal storage disorders
Linhart and Elliott
Heart 2007;93:528-535.
FULL TEXT  

HPLC for Simultaneous Quantification of Total Ceramide, Glucosylceramide, and Ceramide Trihexoside Concentrations in Plasma
Groener et al.
Clin. Chem. 2007;53:742-747.
ABSTRACT | FULL TEXT  

Narrative Review: Fabry Disease
Clarke
ANN INTERN MED 2007;146:425-433.
ABSTRACT | FULL TEXT  

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities
Moore et al.
Proc. Natl. Acad. Sci. USA 2007;104:2873-2878.
ABSTRACT | FULL TEXT  

Enzyme Replacement in Fabry Disease: The Essence Is in the Kidney
Schiffmann
ANN INTERN MED 2007;146:142-144.
FULL TEXT  

Subcortical Damage and Cortical Functional Changes in Men and Women with Fabry Disease: A Multifaceted MR Study.
Gavazzi et al.
Radiology 2006;241:492-500.
ABSTRACT | FULL TEXT  

ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)
Developed in Collaboration With the European Heart et al.
J Am Coll Cardiol 2006;48:e247-e346.
FULL TEXT  

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Writing Committee Members et al.
Europace 2006;8:746-837.
FULL TEXT  

Enzyme-Replacement Therapy With Agalsidase Alfa in Children With Fabry Disease
Ries et al.
Pediatrics 2006;118:924-932.
ABSTRACT | FULL TEXT  

Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Goldstein et al.
Circulation 2006;113:e873-e923.
ABSTRACT | FULL TEXT  

Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Goldstein et al.
Stroke 2006;37:1583-1633.
ABSTRACT | FULL TEXT  

Natural history of Fabry disease in females in the Fabry Outcome Survey
Deegan et al.
J. Med. Genet. 2006;43:347-352.
ABSTRACT | FULL TEXT  

Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting
Schiffmann et al.
Nephrol Dial Transplant 2006;21:345-354.
ABSTRACT | FULL TEXT  

Home treatment for Fabry disease: practice guidelines based on 3 years experience in The Netherlands
Linthorst et al.
Nephrol Dial Transplant 2006;21:355-360.
ABSTRACT | FULL TEXT  

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease
Weidemann et al.
Eur Heart J 2005;26:1221-1227.
ABSTRACT | FULL TEXT  

Urinary Lipid Profiling for the Identification of Fabry Hemizygotes and Heterozygotes
Fuller et al.
Clin. Chem. 2005;51:688-694.
ABSTRACT | FULL TEXT  

Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)
Hoffmann et al.
J. Med. Genet. 2005;42:247-252.
ABSTRACT | FULL TEXT  

Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients
Hagemans et al.
Brain 2005;128:671-677.
ABSTRACT | FULL TEXT  

Pediatric Fabry Disease
Ries et al.
Pediatrics 2005;115:e344-e355.
ABSTRACT | FULL TEXT  

Genetics of Cerebrovascular Disorders
Meschia et al.
Mayo Clin Proc. 2005;80:122-132.
ABSTRACT  

Fabry Disease: A Study of 6 Hemizygous Men and 5 Heterozygous Women With Emphasis on Dermatologic Manifestations
Larralde et al.
Arch Dermatol 2004;140:1440-1446.
ABSTRACT | FULL TEXT  

Fabry Disease: More Than Angiokeratomas
Mohrenschlager et al.
Arch Dermatol 2004;140:1526-1528.
FULL TEXT  

Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors
Yoshimitsu et al.
Proc. Natl. Acad. Sci. USA 2004;101:16909-16914.
ABSTRACT | FULL TEXT  

Immunoquantification of {alpha}-Galactosidase: Evaluation for the Diagnosis of Fabry Disease
Fuller et al.
Clin. Chem. 2004;50:1979-1985.
ABSTRACT | FULL TEXT  

Nephrotic Syndrome Complicating {alpha}-Glucosidase Replacement Therapy for Pompe Disease
Hunley et al.
Pediatrics 2004;114:e532-e535.
ABSTRACT | FULL TEXT  

Results of a Nationwide Screening for Anderson-Fabry Disease among Dialysis Patients
Kotanko et al.
J. Am. Soc. Nephrol. 2004;15:1323-1329.
ABSTRACT | FULL TEXT  

Long-Term Intravenous Treatment of Pompe Disease With Recombinant Human {alpha}-Glucosidase From Milk
Van den Hout et al.
Pediatrics 2004;113:e448-e457.
ABSTRACT | FULL TEXT  

Enzyme replacement therapy improves function of C-, A{delta}-, and A{beta}-nerve fibers in Fabry neuropathy
Hilz et al.
Neurology 2004;62:1066-1072.
ABSTRACT | FULL TEXT  

Improvement of Cardiac Function During Enzyme Replacement Therapy in Patients With Fabry Disease: A Prospective Strain Rate Imaging Study
Weidemann et al.
Circulation 2003;108:1299-1301.
ABSTRACT | FULL TEXT  

Treatment of lysosomal storage disorders
Mehta et al.
BMJ 2003;327:462-463.
FULL TEXT  

{alpha}-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease
Linthorst et al.
Nephrol Dial Transplant 2003;18:1581-1584.
ABSTRACT | FULL TEXT  

{alpha}-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease
Linthorst et al.
Nephrol Dial Transplant 2003;18:1581-1584.
ABSTRACT | FULL TEXT  

Fabry disease: a mimic for obstructive hypertrophic cardiomyopathy?
Ommen et al.
Heart 2003;89:929-930.
FULL TEXT  

Current Therapeutic Strategies for Patients With Polyneuropathies Secondary to Inherited Metabolic Disorders
Burns et al.
Mayo Clin Proc. 2003;78:858-868.
ABSTRACT  

T1 Hyperintensity in the Pulvinar: Key Imaging Feature for Diagnosis of Fabry Disease
Takanashi et al.
Am. J. Neuroradiol. 2003;24:916-921.
ABSTRACT | FULL TEXT  

A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease
Lee et al.
Glycobiology 2003;13:305-313.
ABSTRACT | FULL TEXT  

Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer
Park et al.
Proc. Natl. Acad. Sci. USA 2003;100:3450-3454.
ABSTRACT | FULL TEXT  

Insights Into the Diagnosis and Treatment of Lysosomal Storage Diseases
Wenger et al.
Arch Neurol 2003;60:322-328.
ABSTRACT | FULL TEXT  

Fabry Disease, an Under-Recognized Multisystemic Disorder: Expert Recommendations for Diagnosis, Management, and Enzyme Replacement Therapy
Desnick et al.
ANN INTERN MED 2003;138:338-346.
ABSTRACT | FULL TEXT  

Fabry Disease in Mice Is Associated With Age-Dependent Susceptibility to Vascular Thrombosis
Eitzman et al.
J. Am. Soc. Nephrol. 2003;14:298-302.
ABSTRACT | FULL TEXT  

Enzyme replacement therapy for Fabry disease: proving the clinical benefit
Breunig and Wanner
Nephrol Dial Transplant 2003;18:7-9.
FULL TEXT  

Enzyme replacement therapy in Anderson-Fabry's disease: beneficial clinical effect on vital organ function
De Schoenmakere et al.
Nephrol Dial Transplant 2003;18:33-35.
ABSTRACT | FULL TEXT  

Production in yeast of {alpha}-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease
Chiba et al.
Glycobiology 2002;12:821-828.
ABSTRACT | FULL TEXT  

Renal involvement in an Anderson-Fabry heterozygote
Kingdon et al.
Postgrad. Med. J. 2002;78:759-759.
FULL TEXT  

Cardiac manifestations of Anderson-Fabry disease in heterozygous females
Kampmann et al.
J Am Coll Cardiol 2002;40:1668-1674.
ABSTRACT | FULL TEXT  

Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer
Takahashi et al.
Proc. Natl. Acad. Sci. USA 2002;99:13777-13782.
ABSTRACT | FULL TEXT  

New developments in the management of Anderson-Fabry disease
MEHTA
QJM 2002;95:647-653.
ABSTRACT | FULL TEXT  

Neurological presentation of Fabry's disease in a 52 year old man
Mohanraj et al.
J. Neurol. Neurosurg. Psychiatry 2002;73:340-342.
ABSTRACT | FULL TEXT  

Muscle as a putative producer of acid {alpha}-glucosidase for glycogenosis type II gene therapy
Martin-Touaux et al.
Hum Mol Genet 2002;11:1637-1645.
ABSTRACT | FULL TEXT  

Natural History and Treatment of Renal Involvement in Fabry Disease
Branton et al.
J. Am. Soc. Nephrol. 2002;13:S139-143.
FULL TEXT  

End-Stage Renal Disease in Patients with Fabry Disease
Obrador et al.
J. Am. Soc. Nephrol. 2002;13:S144-146.
FULL TEXT  

Cardiac Involvement in Anderson-Fabry Disease
Kampmann et al.
J. Am. Soc. Nephrol. 2002;13:S147-149.
FULL TEXT  

Brain-directed gene therapy for lysosomal storage disease: Going well beyond the blood- brain barrier
Sly and Vogler
Proc. Natl. Acad. Sci. USA 2002;99:5760-5762.
FULL TEXT  

Prevalence of Anderson-Fabry Disease in Male Patients With Late Onset Hypertrophic Cardiomyopathy
Sachdev et al.
Circulation 2002;105:1407-1411.
ABSTRACT | FULL TEXT  

Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males
MacDermot et al.
J. Med. Genet. 2001;38:750-760.
ABSTRACT | FULL TEXT  

Skin Manifestations of Fabry Disease
Mohrenschlager et al.
JAMA 2001;286:1315-1315.
FULL TEXT  

Enzyme therapy for lysosomal acid lipase deficiency in the mouse
Du et al.
Hum Mol Genet 2001;10:1639-1648.
ABSTRACT | FULL TEXT