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
Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, 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: 10.7326/0003-4819-138-4-200302180-00014
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Published: Ann Intern Med. 2003;138(4):338-346.
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.
. Electron µgraph showing the vascular endothelium of a small vessel from a patient with Fabry disease. Note the electron-dense vesicles (lysosomes) in the endothelium containing undegraded glycosphingolipid. The progressive lysosomal accumulation in the vascular endothelium leads to ischemia and infarction of these vessels. . Electrocardiogram of a 41-year-old man with classic Fabry disease showing sinus bradycardia with short PR interval (88 msec) and left ventricular hypertrophy with QRS widening and a repolarization abnormality.
and . Angiokeratomas. These characteristic dark red to blue-black angiectases are most often found in clusters between the umbilicus and thigh. The lesions are nonblanching, become larger and more numerous with age, and range in size from pinhead to several millimeters. . Whorled corneal opacity that does not affect vision. This opacity, seen only by using slit-lamp microscopy, is found in almost all males with Fabry disease and in 70% to 90% of carrier females; it is often more distinctive in females. Note the whorl-like rays emanating from a single vertex.
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