Biomarkers and Imaging Findings of Anderson-Fabry Disease-What We Know Now.

Idalina Beirão,Fernando Silva,Francisco Laranjeira,Patrício Aguiar,Ana Marta Gomes,Ana Cabrita,Márcia Torres

doi:10.3390/diseases5020015

Abstract

Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients.

Highlights

Anderson–Fabry disease (AFD), an X-linked lysosomal storage disorder, is caused by the deficiency or the absence of the alpha-galactosidase A (α-Gal-A), which leads to an accumulation of globotriaosylceramide/ceramide trihexoside (Gb3) and other glycosphingolipids in the lysosomes of several cells types, mainly the endothelial, neuronal, cardiac and renal cells
The first study [9] demonstrated that the plasma Lyso-Gb3 was not increased in 11 patients carrying GLA mutations not unequivocally linked to AFD, namely p.R112H and p.P60L. These results suggest that measurement of Lyso-Gb3 in plasma could be an additional useful evaluation for the confirmation of AFD in individuals with GLA
In a prospective observational study with 66 patients performing an echocardiogram at the baseline and periodically, found an increase in interventricular septum thickness associated with the decrease of the Doppler tissue imaging (DTI) velocities [63]

Summary

Introduction

Anderson–Fabry disease (AFD), an X-linked lysosomal storage disorder, is caused by the deficiency or the absence of the alpha-galactosidase A (α-Gal-A), which leads to an accumulation of globotriaosylceramide/ceramide trihexoside (Gb3) and other glycosphingolipids in the lysosomes of several cells types, mainly the endothelial, neuronal, cardiac and renal cells. Some patients present a late-onset attenuated phenotypes, with the predominant involvement of an organ [1]. The diagnosis of AFD is established by the determination of α-Gal-A activity and/or by the GLA gene (gene coding for α-galactosidase A) analysis. In male patients with classical manifestations of the disease, the diagnosis can be confirmed if the activity of α-Gal-A is not detectable or less than 5% of the expected value. In male individuals with attenuated phenotypes and in heterozygous female patients, the residual enzyme activity can be significant ( less than the normal for the general population), and, in these cases, the GLA gene analysis is required for a definitive diagnosis [2,3]

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