Robert J. Desnick, PhD, MD; Roscoe Brady, MD; John Barranger, MD, PhD; Allan J. Collins, MD; Dominique P. Germain, MD, PhD; Martin Goldman, MD; Gregory Grabowski, MD; Seymour Packman, MD; William R. Wilcox, MD, PhD
Grant Support: By a grant from the National Institutes of Health (5 R37 DK34045) and the Genzyme Corporation, Cambridge, Massachusetts.
Acknowledgment: The authors thank Lisa Underhill for author interviews and writing assistance.
Potential Financial Conflicts of Interest: Consultancies: R.J. Desnick (Genzyme Corp.), R. Brady (Genzyme Corp., Transkaryotic Therapies, Inc.), J. Barranger (Genzyme Corp.), D.P. Germain (Genzyme Corp., Transkaryotic Therapies, Inc.), G. Grabowski (Genzyme Corp., Transkaryotic Therapies, Inc.), S. Packman (Genzyme Corp., Transkaryotic Therapies, Inc.), W.R. Wilcox (Genzyme Corp.); Honoraria: J.A. Barranger (Genzyme Corp.), A.J. Collins (Genzyme Corp.), D.P. Germain (Genzyme Corp., Transkaryotic Therapies, Inc.), G. Grabowski (Genzyme Corp., Transkaryotic Therapies, Inc., Profound); W.R. Wilcox (Genzyme Corp.); Stock ownership or options (other than mutual funds): R.O. Brady (Genzyme Corp.); Grants received: R.J. Desnick (Genzyme Corp.), J.A. Barranger (Genzyme Corp.), A.J. Collins (Genzyme Corp.), G. Grabowski (Genzyme Corp.), W.R. Wilcox (Genzyme Corp.); Grants pending: J.A. Barranger (Genzyme Corp.), W.R. Wilcox (Genzyme Corp.); Patents pending: R.J. Desnick (patents from Mt. Sinai Medical Center licensed to Genzyme Corp.), J.A. Barranger (Genzyme Corp.); Royalties: J.A. Barranger (Genzyme Corp.).
Requests for Single Reprints: Robert J. Desnick, PhD, MD, Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, New York, NY 10029; e-mail: email@example.com.
Current Author Addresses: Dr. Desnick: Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, New York, NY 10029.
Dr. Brady: National Institute of Neurological Disorders and Stroke, Building 10, Room 3D04, National Institutes of Health, 10 Center CR MSC 1260, Bethesda, MD 20892-1260.
Dr. Barranger: Department of Human Genetics, University of Pittsburgh Medical Center, Pittsburgh, PA 15261.
Dr. Collins: University of Minnesota, 914 S. 8th Street, Suite D206, Minneapolis, MN 55404.
Dr. Germain: Unit de Gntique Clinique, Hpital Europen Georges Pompidou, Paris, France.
Dr. Goldman: Mount Sinai Medical CenterCardiology, One Gustave Levy Place, New York, NY 10029.
Dr. Grabowski: Director Human Genetics, Children's Hospital Medical Center, Elland and Bethesda Avenues, Cincinnati, OH 45229-2899.
Dr. Packman: Division of Medical Genetics, Department of Pediatrics, Room U-585k, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143-0748.
Dr. Wilcox: Cedars-Sinai Medical Center, Division of Medical Genetics, SSB-3, 8700 Beverly Boulevard, Los Angeles, CA 90048.
Fabry disease (-galactosidase A deficiency) is an X-linked recessive lysosomal storage disorder. Although the disease presents in childhood and culminates in cardiac, cerebrovascular, and end-stage renal disease, diagnosis is often delayed or missed. This paper reviews the key signs and symptoms of Fabry disease and provides expert recommendations for diagnosis, follow-up, medical management, and the use of enzyme replacement therapy. Recommendations are based on reviews of the literature on Fabry disease, results of recent clinical trials, and expertise of the authors, all of whom have extensive clinical experience with Fabry disease and lysosomal storage disorders and represent subspecialties involved in treatment.
All males and female carriers affected with Fabry disease should be followed closely, regardless of symptoms or treatment status. Clinical trials have shown that recombinant human -galactosidase A replacement therapythe only disease-specific therapy currently available for Fabry diseaseis safe and can reverse substrate storage in the lysosome, the pathophysiologic basis of the disease. Enzyme replacement therapy in all males with Fabry disease (including those with end-stage renal disease) and female carriers with substantial disease manifestations should be initiated as early as possible. Additional experience is needed before more specific recommendations can be made on optimal dosing regimens for reversal; maintenance; and prevention of disease manifestations in affected males, symptomatic carrier females, children, and patients with compromised renal function.
Distinctive laboratory findings in Fabry disease. AB
Distinctive clinical features of Fabry disease. ABC
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Desnick RJ, Brady R, Barranger J, et al. Fabry Disease, an Under-Recognized Multisystemic Disorder: Expert Recommendations for Diagnosis, Management, and Enzyme Replacement Therapy. Ann Intern Med. 2003;138:338–346. doi: https://doi.org/10.7326/0003-4819-138-4-200302180-00014
Download citation file:
Published: Ann Intern Med. 2003;138(4):338-346.
Encephalopathy, Guidelines, Neurology.
Results provided by:
Copyright © 2019 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use