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BioMed Research International
Volume 2015 (2015), Article ID 504784, 5 pages
Research Article

High Variability of Fabry Disease Manifestations in an Extended Italian Family

1Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy
2Internal Medicine, Nephrology and Dialysis Unit, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
3Institute of Neurological Sciences (ISN), National Research Council, 95126 Catania, Italy
4Complex Operative Unit of Neurology, S. Antonio Abate Hospital, 91016 Trapani, Italy
5Department of Neurology, “R. Guzzardi” Hospital, ASP Ragusa, Vittoria, 97019 Ragusa, Italy
6Department of Biopathology and Medical and Forensic Biotechnology, Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy
7Cardio-Thorax-Vascular and Transplant Department, University of Catania, 95125 Catania, Italy

Received 11 December 2014; Revised 11 March 2015; Accepted 24 March 2015

Academic Editor: Janusz Blasiak

Copyright © 2015 Giuseppe Cammarata et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.