International Journal of Molecular Sciences (Nov 2018)
Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?
- Giovanni Duro,
- Carmela Zizzo,
- Giuseppe Cammarata,
- Alessandro Burlina,
- Alberto Burlina,
- Giulia Polo,
- Simone Scalia,
- Roberta Oliveri,
- Serafina Sciarrino,
- Daniele Francofonte,
- Riccardo Alessandro,
- Antonio Pisani,
- Giuseppe Palladino,
- Rosa Napoletano,
- Maurizio Tenuta,
- Daniele Masarone,
- Giuseppe Limongelli,
- Eleonora Riccio,
- Andrea Frustaci,
- Cristina Chimenti,
- Claudio Ferri,
- Federico Pieruzzi,
- Maurizio Pieroni,
- Marco Spada,
- Cinzia Castana,
- Marina Caserta,
- Ines Monte,
- Margherita Stefania Rodolico,
- Sandro Feriozzi,
- Yuri Battaglia,
- Luisa Amico,
- Maria Angela Losi,
- Camillo Autore,
- Marco Lombardi,
- Carmine Zoccali,
- Alessandra Testa,
- Maurizio Postorino,
- Renzo Mignani,
- Elisabetta Zachara,
- Antonello Giordano,
- Paolo Colomba
Affiliations
- Giovanni Duro
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Carmela Zizzo
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Giuseppe Cammarata
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Alessandro Burlina
- Neurological Unit, St Bassiano Hospital, 36061 Bassano del Grappa, Italy
- Alberto Burlina
- Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children’s Health, University Hospital of Padova, 35128 Padova, Italy
- Giulia Polo
- Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children’s Health, University Hospital of Padova, 35128 Padova, Italy
- Simone Scalia
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Roberta Oliveri
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Serafina Sciarrino
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Daniele Francofonte
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Riccardo Alessandro
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- Antonio Pisani
- Department of Public Health, Nephrology Unit, University of Naples “Federico II”, 80131 Naples, Italy
- Giuseppe Palladino
- Nephrology Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
- Rosa Napoletano
- Neurology Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
- Maurizio Tenuta
- Neurology Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
- Daniele Masarone
- Division of Cardiology, Second University of Naples, Presidio Monaldi, 80131 Naples, Italy
- Giuseppe Limongelli
- Division of Cardiology, Second University of Naples, Presidio Monaldi, 80131 Naples, Italy
- Eleonora Riccio
- Department of Public Health, Nephrology Unit, University of Naples “Federico II”, 80131 Naples, Italy
- Andrea Frustaci
- Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and GeriatricSciences, Sapienza University, 00161 Rome, Italy
- Cristina Chimenti
- Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and GeriatricSciences, Sapienza University, 00161 Rome, Italy
- Claudio Ferri
- Nephrology Unit, Hospital of L’Aquila, 67100 L’Aquila, Italy
- Federico Pieruzzi
- Nephrology Unit, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Maurizio Pieroni
- Cardiovascular Department, San Donato Hospital, 52100 Arezzo, Italy
- Marco Spada
- Department of Pediatrics, Division of Metabolic Diseases, Turin University Hospital, 10126 Turin, Italy
- Cinzia Castana
- Paediatric Hospital “G. Di Cristina”, ARNAS Civico, 90134 Palermo, Italy
- Marina Caserta
- Paediatric Hospital “G. Di Cristina”, ARNAS Civico, 90134 Palermo, Italy
- Ines Monte
- Cardiology Department Echocardiography Laboratory, Department of Cardiothoracic and Vascular, Policlinico Vittorio Emanuele, Catania University, 95124 Catania, Italy
- Margherita Stefania Rodolico
- Institute of Neurological Sciences (ISN), National Research Council, 95126 Catania, Italy
- Sandro Feriozzi
- Nephrology and Dialysis Unit, Belcolle Hospital, 01100 Viterbo, Italy
- Yuri Battaglia
- Department of Specialized Medicine, Division of Nephrology and Dialysis, St. Anna Hospital-University, 44124 Ferrara, Italy
- Luisa Amico
- Unit of Nephrology, Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy
- Maria Angela Losi
- Department of Advanced Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
- Camillo Autore
- Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00161 Rome, Italy
- Marco Lombardi
- Nephrology and Dialysis Unit, Mugello Hospital, A.S. Toscana Centro, Borgo San Lorenzo, 50032 Firenze, Italy
- Carmine Zoccali
- Institute of Clinical Physiology, Division of Nephrology, National Research Council, 89129 Reggio Calabria, Italy
- Alessandra Testa
- Institute of Clinical Physiology, Division of Nephrology, National Research Council, 89129 Reggio Calabria, Italy
- Maurizio Postorino
- Nephrology Unit, Grande Ospedale Metropolitano Reggio Calabria, 89124 Reggio Calabria, Italy
- Renzo Mignani
- Department of Nephrology, Infermi Hospital, 47923 Rimini, Italy
- Elisabetta Zachara
- Cardiac Arrhythmia Center and Cardiomyopathies Unit, San Camillo-Forlanini Hospital, 00152 Roma, Italy
- Antonello Giordano
- Department of Neurology, Guzzardi Hospital, 97019 Vittoria, Italy
- Paolo Colomba
- Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, 90146 Palermo, Italy
- DOI
- https://doi.org/10.3390/ijms19123726
- Journal volume & issue
-
Vol. 19,
no. 12
p. 3726
Abstract
Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. α-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, α-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.
Keywords