title: High variability of Fabry disease manifestations in an extended Italian family.
abstract: 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.
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cammarata
authors.affiliation: Internal Medicine, Nephrology and Dialysis Unit, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fatuzzo
authors.affiliation: Institute of Neurological Sciences (ISN), National Research Council, 95126 Catania, Italy.
authors.forename: Margherita Stefania
authors.initials: MS
authors.lastname: Rodolico
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colomba
authors.affiliation: Complex Operative Unit of Neurology, S. Antonio Abate Hospital, 91016 Trapani, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sicurella
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy ; Department of Neurology, "R. Guzzardi" Hospital, ASP Ragusa, Vittoria, 97019 Ragusa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Iemolo
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Zizzo
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy ; Department of Biopathology and Medical and Forensic Biotechnology, Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy.
authors.forename: Riccardo
authors.identifier: 0000-0002-9935-1040
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bartolotta
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, 90146 Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Duro
authors.affiliation: Cardio-Thorax-Vascular and Transplant Department, University of Catania, 95125 Catania, Italy.
authors.forename: Ines
authors.identifier: 0000-0001-7059-7525
authors.initials: I
authors.lastname: Monte
mesh_terms: D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase