Italian Anderson Fabry Disease Cardiovascular Registry (RICMAF)

January 28, 2025 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

The RICMAF Study is an observational, multicenter, non-pharmacological study conducted in Italy.

Although Anderson-Fabry Disease (AFD) is rare, it is likely underdiagnosed due to its nonspecific symptoms, leading to delays in proper treatment. The RICMAF Study aims to improve understanding of AFD, especially its cardiac manifestations, which are a major cause of mortality. By gathering data from a large, nationwide patient registry, this study seeks to answer key questions about AFD's clinical course and improve patient outcomes.

The primary goals of the RICMAF Study are:

To analyze the clinical profile, prevalence, and incidence of AFD, along with patients' family history and disease progression.
To identify early markers of cardiac involvement and predictors of cardiovascular complications to personalize care.
To investigate the relationship between genetic mutations, clinical presentation, and prognosis.
To find early indicators of organ damage through laboratory and imaging tests.

All patients diagnosed with AFD following international guidelines are eligible.

Study Overview

Status

Recruiting

Conditions

Fabry Disease

Detailed Description

Introduction
Anderson-Fabry Disease (AFD) is a multisystemic lysosomal storage disorder with X-linked inheritance (Online Mendelian Inheritance in Man [OMIM] number 301500) caused by a total or partial deficiency of the enzyme α-galactosidase A (α-Gal A), encoded by the GLA gene (Xq22.1). The deficiency of α-Gal A leads to the accumulation of neutral glycosphingolipids, particularly globotriaosylceramide (Gb3) and galactosylceramide, in various cell types and tissues. The continuous accumulation of these molecules results in progressive cellular dysfunction, triggering inflammatory and pro-fibrotic phenomena that cause organ dysfunction.
The clinical manifestations and age of onset of the disease are highly variable, and symptoms/signs often appear only after a degree of irreversible damage has already occurred. The classic form of AFD is the most severe clinical phenotype and predominantly affects males with null or minimal residual enzymatic activity (<1% of normal values). Symptoms begin early during childhood or adolescence and include acroparesthesias, angiokeratomas, telangiectasias, gastrointestinal disturbances, corneal alterations (cornea verticillata), proteinuria, renal insufficiency, hypo/hyperhidrosis, and hearing loss. Later in adulthood, progressive cardiac and cerebrovascular involvement may occur.
Patients with atypical or late-onset variants generally develop the disease later (from the third to the seventh decade of life) compared to those with the classic form. The clinical picture is generally dominated by the involvement of a single organ, most frequently the heart. The measurement of residual enzymatic activity of α-Gal A is sufficient to establish a diagnosis in males. However, it is important to identify the specific genetic mutation to determine the disease phenotype and exclude benign polymorphisms that may cause reduced enzymatic activity levels. In females, genetic diagnosis is indispensable, as residual enzymatic activity often falls within the normal range.
The treatment of AFD is based on compensating for the deficient enzymatic activity through enzyme replacement therapy (ERT) and managing the disease's symptoms and complications. More recently, an oral chaperone therapy capable of increasing residual enzymatic activity has been approved, though it is only effective for certain mutation types. Given the multisystemic involvement in AFD patients, longitudinal multispecialty evaluation is necessary, including cardiology, nephrology, neurology, dermatology, ophthalmology, and otorhinolaryngology assessments.
Cardiac involvement is the main prognostic factor, with cardiovascular death being the leading cause of mortality. Manifestations include unexplained ventricular hypertrophy (which must be differentiated from the more common sarcomeric hypertrophic cardiomyopathy), valvular diseases, angina pectoris due to coronary microcirculation dysfunction, conduction abnormalities (which may require permanent pacemaker implantation), and supraventricular and ventricular tachyarrhythmias. Cardiological evaluation is recommended annually or earlier if clinically indicated, including systemic blood pressure assessment, ECG, echocardiography, and arrhythmia detection via 24-hour Holter ECG monitoring (or extended monitoring [e.g., loop recorder] when deemed appropriate).
In recent years, cardiac magnetic resonance imaging (CMR) has become a key investigation not only for diagnosing the disease but also for its follow-up and for evaluating the response to therapy. CMR allows for accurate assessment of cardiac chamber volumes and function and enables tissue characterization using gadolinium-based contrast agents and advanced T1 and T2 mapping techniques. Endomyocardial biopsy is now reserved for patients with genetic variants of uncertain significance (VUS), high residual enzymatic activity (>10%), and/or low lyso-Gb3 levels to confirm or exclude AFD as the cause of left ventricular hypertrophy.
Study Background
AFD is a rare disease, and the estimated prevalence of the classic forms was previously reported to range between 1:40,000 and 1:117,000. However, these data likely represent an underestimation, as the manifestations are nonspecific, and AFD is often not considered among diagnostic hypotheses, leading to misdiagnosis or delayed diagnosis. Supporting this, recent genetic newborn screening programs not based on symptom development suggest that AFD may be far more common than previously suspected.
Although the last decade has seen increasing understanding of the disease's pathophysiological mechanisms, natural history, and the efficacy and limitations of current therapeutic options, many unanswered questions remain. This highlights the need to create an Italian cardiological registry for Anderson-Fabry Disease to bring together various centers located in different regions nationwide to collect the largest possible number of patients.
Study Objectives
- Evaluate the clinical profile, prevalence, and incidence of the disease (relative to the general population), as well as the family and natural history of AFD patients, particularly the incidence of morbidity/mortality during follow-up.
- Identify clinical and instrumental predictors of cardiovascular morbidity and mortality to improve risk stratification and personalize the most appropriate management program for each patient.
- Assess the correlation between genetic findings, phenotype, and prognosis, with particular emphasis on differences in cardiac involvement between classic and late-onset variants with cardiac involvement.
- Investigate serological/tissue markers and instrumental indicators of early organ damage.
Study Plan
4.1 Study Population All patients affected by Anderson-Fabry Disease (AFD), diagnosed according to current international guidelines, will be included in the study upon obtaining informed consent. Based on the estimated prevalence of the disease, the study plans to enroll approximately 800 patients over 10 years.
Inclusion Criteria:
- Patients diagnosed with Anderson-Fabry Disease.
- Age ≥ 2 years at the time of diagnosis.
- Informed consent obtained from the patient or their parent/legal guardian.
Exclusion Criteria:
- None.
4.2 Study Design
The study is an Italian multicenter, observational, retrospective, and prospective, non-pharmacological study. Participation will be proposed consecutively to all patients with AFD attending the participating centers, both as outpatients and inpatients.
Structured data collection for objective evaluation will occur through a dedicated electronic archive, gathering data from the observation period between January 1, 1981, and December 31, 2031. This electronic archive may be used to obtain or confirm new scientific evidence regarding AFD, particularly focusing on diagnosis, prognosis, and therapy.
Data entry into the electronic archive will be based on the review of medical records (outpatient or inpatient), collecting information about demographics, past and recent medical history, family history, genetic investigations, instrumental assessments, signs and symptoms of the disease, and therapy.
Data Collection Modes:
- Prospective Phase: Patients will be enrolled during hospitalization or at the first outpatient visit after obtaining free and informed consent. Patients will subsequently undergo clinical evaluations, instrumental investigations, and therapeutic interventions as per clinical necessity and standard care practices. A minimum follow-up duration is not required; even a single evaluation suffices for inclusion in the archive.
- Retrospective Phase: Data from patients will be retrospectively collected starting from January 1, 1981. In this phase, no predefined observation period is required. If the patient is no longer being followed, a substitute declaration of consent for retrospective observational studies will be used to utilize clinical/instrumental data excluding genetic data.
In all cases where it is possible to provide adequate information, particularly when patients return to care centers for health services or follow-up visits, their consent for data processing must be obtained.
4.3 Discontinuation of Participation
Patients may choose to discontinue their participation in the study at any time.
4.4 Visits and Assessments
Specialist visits, laboratory tests, genetic analyses, and instrumental evaluations to which patients are or will be subjected fall within the normal care pathway, in line with the standard of care. The data collected will derive from initial and follow-up visits or hospitalizations that are part of standard clinical practice.
Data Management and Statistical Analysis
5.1 Data Collection Methods Systematic data collection will occur through the creation of a dedicated electronic archive, collecting data for the observation period between January 1, 1981, and December 31, 2031. Clinical data required by the protocol will be pseudonymized and entered by designated staff into an electronic Case Report Form (eCRF) managed via the REDCap platform. The eCRF in REDCap will be developed and managed following the procedure outlined in the "Operational Instruction for the Management and Use of the REDCap Platform" (IOA119).
The Principal Investigator must specify the personnel delegated for data management and their respective roles in the study in the Delegation Log. Collected data will be derived from standard care medical records, with no study-specific assessments performed.
5.2 Statistical Methods The collected data will include demographics (age, gender), medical history, instrumental data (ECG, echocardiography, cardiac MRI, stress tests, 24-hour Holter ECG, biopsies), laboratory data (CBC, platelets, renal and liver function, BNP, troponin, serum electrolytes, urinalysis, etc.), genetic investigation findings, and follow-up data.
The results of the analysis will be processed statistically in anonymous form to derive the study objectives. Data will be presented using descriptive statistics:
- Qualitative parameters will be expressed as numbers or percentages and analyzed using Chi-square or Fisher's exact test.
- Quantitative parameters will be expressed as mean and standard deviation or as median and interquartile range, with comparisons between patients performed using parametric tests (ANOVA, Student's t-test) or non-parametric tests (Kruskal-Wallis and Mann-Whitney U tests).
A p-value ≤ 0.05 will be considered statistically significant. Statistical analyses will be conducted using Stata/SE v.14.2 for Windows.
Administrative Procedures

Good Clinical Practice Guidelines This study will be conducted in compliance with Good Clinical Practice (GCP) guidelines [ICH Harmonized Tripartite Guidelines for GCP 1996 Directive 91/507/EEC; D.M. 15.7.1997], the Declaration of Helsinki, and national regulations governing clinical research. By signing the protocol, the investigator agrees to adhere to the procedures and instructions contained therein and to conduct the study according to GCP, the Declaration of Helsinki, and national regulations on clinical trials.

Protocol Amendments or Study Modifications Any protocol modifications will be implemented as formal amendments. No protocol modifications are allowed during the study period. Any unforeseen changes in study conduct will be documented in the "Clinical Study Report."

Ethical Committee Approval The study protocol, any amendments, informed consent forms, and patient information must be approved by the Ethics Committee. For amendments, the Investigator may immediately implement changes to ensure patient safety and must notify the Ethics Committee within 10 working days.

Consent Management Patients will be enrolled during hospitalization or outpatient visits, and each participant must sign an informed consent form.

For the prospective phase, consent will be obtained during the standard diagnostic process.
For the retrospective phase, concerning previously collected data, informed consent will be sought during follow-up visits. For deceased or unreachable patients, data will be processed without consent based on General Authorization No. 146/2019 from the Privacy Authority, excluding genetic data.

Documentation Archive.

The Investigator is responsible for archiving and storing essential study documents before, during, and after the study in compliance with applicable regulations and GCP. Data in the CRF will be strictly anonymous, and subjects will be identified only by a number and initials.

Publication of Results Data publication will occur after processing during the data collection period or after the final update of the archive.

Costs No additional costs are foreseen for conducting this study. Clinical evaluations and instrumental examinations are routinely performed in these patients as part of standard clinical practice.

Study Type

Observational

Enrollment (Estimated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Elena Biagini, MD, PhD
Phone Number: +39051214483
Email: elena.biagini@aosp.bo.it

Study Contact Backup

Name: Silvia Palmieri, M. Sc.
Phone Number: +39051214483
Email: silvia.palmieri@aosp.bo.it

Study Locations

Italy
- - Caserta, Italy, 81100
    - Not yet recruiting
    - AORN "Sant'Anna e San Sebastiano" di Caserta
    - Contact:
      
      Paolo Calabrò, MD
      
      Phone Number: +390823.232395
      
      Email: paolo.calabro@unicampania.it
  - Catanzaro, Italy, 88100
    - Not yet recruiting
    - Azienda Ospedaliero - Universitaria "Mater Domini
    - Contact:
      
      Ciro Indolfi, MD
      
      Phone Number: +390961364753
      
      Email: indolfi@unicz.it
  - Cosenza, Italy, 87100
    - Not yet recruiting
    - Azienda Ospedaliera di Cosenza Università della Calabria
    - Contact:
      
      Antonio Curcio, MD
      
      Phone Number: +3909613694401
      
      Email: antonio.curcio@aocs.it
  - Genova, Italy
    - Not yet recruiting
    - IRCCS Ospedale Policlinico San Martino
    - Contact:
      
      Marco Canepa, MD
      
      Phone Number: +390105557199
      
      Email: marco.canepa@unige.it
  - Napoli, Italy, 80131
    - Recruiting
    - AO Dei Colli - Ospedale Monaldi
    - Contact:
      
      Giuseppe Limongelli, MD
      
      Phone Number: +390817065187
      
      Email: giuseppe.limongelli@unicampania.it
  - Napoli, Italy, 80131
    - Not yet recruiting
    - AOU Policlinico
    - Contact:
      
      Eduardo Bossone, MD
      
      Phone Number: 0000
      
      Email: eduardo.bossone@unina.it
  - Parma, Italy, 43126
    - Not yet recruiting
    - Azienda Ospedaliero-Universitaria di Parma
    - Contact:
      
      Federico Barocelli, MD
      
      Phone Number: +393386353160
      
      Email: fbarocelli@ao.pr.it
  - Piacenza, Italy, 29121
    - Not yet recruiting
    - Azienda Ospedaliera "Guglielmo da Saliceto" di Piacenza
    - Contact:
      
      Francesco Di spigno, MD
      
      Phone Number: +393403515464
      
      Email: francesco.dispigno@yahoo.com
  - Reggio Calabria, Italy
    - Not yet recruiting
    - Ospedale Metropolitano Riuniti "Bianchi - Melacrino - Morelli
    - Contact:
      
      Carmelo Rao, MD
      
      Phone Number: +390965393750
      
      Email: massimo.rao@libero.it
  - Reggio Emilia, Italy, 42123
    - Recruiting
    - Arcispedale S.Maria Nuova
    - Contact:
      
      Chiara Leuzzi, MD
      
      Phone Number: +393473067153
      
      Email: chiara.leuzzi@ausl.re.it
  - Rimini, Italy, 47923
    - Not yet recruiting
    - Ospedale degli Infermi di Rimini, AUSL Romagna
    - Contact:
      
      Francesca Marzo, MD
      
      Phone Number: 00
      
      Email: francesca.marzo@auslromagna.it
  - Roma, Italy, 00169
    - Not yet recruiting
    - Policlinico Casilino
    - Contact:
      
      Chiara Lanzillo, MD
      
      Phone Number: 0000
      
      Email: chiaralanzillo@hotmail.com
  - Roma, Italy, 00133
    - Not yet recruiting
    - Policlinico "Tor Vergata"
    - Contact:
      
      Francesco Barilla, MD
      
      Phone Number: 000
      
      Email: francesco.barilla@uniroma2.it
  - Roma, Italy, 00136
    - Recruiting
    - Policlinico Gemelli
    - Contact:
      
      Francesca Graziani, MD
      
      Phone Number: +390630154639
      
      Email: francesca.graziani@policlinicogemelli.it
  - Roma, Italy, 00161
    - Not yet recruiting
    - Policlinico Umberto I - Università Sapienza
    - Contact:
      
      Cristina Chimenti, MD
      
      Phone Number: +39338 6159124
      
      Email: Cristina.chimenti@uniroma1.it
  - Roma, Italy, 00189
    - Not yet recruiting
    - Ospedale Sant'Andrea
    - Contact:
      
      Maria Beatrice Musumeci, MD
      
      Phone Number: +390633775868
      
      Email: Beatrice.musumeci@gmail.com
  - Roma, Italy
    - Not yet recruiting
    - San Camillo Forlanini
    - Contact:
      
      Federica Re, MD
      
      Phone Number: +390658704539
      
      Email: re.federica77@gmail.com
  - Salerno, Italy, 84131
    - Not yet recruiting
    - Ospedale S.Giovanni di Dio e Ruggì d'Aragona
    - Contact:
      
      Rodolfo Citro, MD
      
      Phone Number: +39089673377
      
      Email: rodcitro@unisa.it
  - Udine, Italy, 33100
    - Not yet recruiting
    - Azienda Sanitaria Universitaria Friuli Centrale
    - Contact:
      
      Massimo Imazio, MD
      
      Phone Number: 000
      
      Email: massimo_imazio@yahoo.it
- Abruzzo/Chieti
  - Chieti, Abruzzo/Chieti, Italy, 66100
    - Not yet recruiting
    - ASL 2 Chieti - Ospedale Policlinico SS. Annunziata
    - Contact:
      
      Sabina Gallina, MD
      
      Phone Number: +390871358597
      
      Email: sabina.gallina@unich.it
- Basilicata/Potenza
  - Potenza, Basilicata/Potenza, Italy, 85100
    - Not yet recruiting
    - Azienda Ospedaliera Regionale S.Carlo
    - Contact:
      
      Eugenio Stabile, MD
      
      Phone Number: +390971613526
      
      Email: eugeniostabile@gmail.com;
- EmiliaRomagna/Bologna
  - Bologna, EmiliaRomagna/Bologna, Italy, 40138
    - Recruiting
    - IRCCS Azienda Ospedaliero-Universitaria di Bologna
    - Contact:
      
      Silvia Palmieri, M. Sc.
      
      Phone Number: +39051214483
      
      Email: silvia.palmieri@aosp.bo.it
    - Contact:
      
      Elena Biagini, MD, PhD
      
      Phone Number: +390512144483
      
      Email: elena.biagini@aosp.bo.it
    - Contact:
      
      Raffaello Ditaranto, MD, PhD
    - Contact:
      
      Vanda Parisi, MD
    - Contact:
      
      Maria Alessandra Schiavo, MD
    - Contact:
      
      Elena Biagini, MD, PhD
- Lombardia/Bergamo
  - Bergamo, Lombardia/Bergamo, Italy, 24127
    - Recruiting
    - Asst Papa Giovanni Xxiii
    - Contact:
      
      Giovanni Quarta, MD
      
      Phone Number: 000
      
      Email: giovanni.quarta@yahoo.it
- Lombardia/Brescia
  - Brescia, Lombardia/Brescia, Italy, 25123
    - Not yet recruiting
    - U.O.Cardiologia Spetali Civili 1
    - Contact:
      
      Savina Nodari, MD
      
      Phone Number: +390303996800
      
      Email: savina.nodari@unibs.it
- Lombardia/Milano
  - Milano, Lombardia/Milano, Italy, 20122
    - Not yet recruiting
    - IRCCS Ospedale Maggiore Policlinico di Milano
    - Contact:
      
      Irene Motta, MD
      
      Phone Number: +390255033548
      
      Email: irene.motta@unimi.it
  - Milano, Lombardia/Milano, Italy, 20126
    - Not yet recruiting
    - IRCCS San Gerardo dei Tintori - S.C. Nefrologia, Monza - Università di Milano Bicocca
    - Contact:
      
      Federico Pieruzzi, MD
      
      Phone Number: +390392339385
      
      Email: federico.pieruzzi@unimib.it
  - Milano, Lombardia/Milano, Italy, 20138
    - Recruiting
    - Centro Cardiologico Monzino
    - Contact:
      
      Gianluca Pontone, MD
      
      Phone Number: +390258002574
      
      Email: gianluca.pontone@cardiologicomonzino.it
  - Milano, Lombardia/Milano, Italy, 20162
    - Not yet recruiting
    - Ospedale Niguarda
    - Contact:
      
      Piero Gentila, MD
      
      Phone Number: +39 02 64447791
      
      Email: Piero.Gentile@ospedaleniguarda.it
  - San Donato Milanese, Lombardia/Milano, Italy, 20097
    - Not yet recruiting
    - IRCCS Policlinico San Donato
    - Contact:
      
      Antonia Camporeale, MD
      
      Phone Number: +360252774376
      
      Email: Antonia.camporeale@grupposandonato.it
- Marche/Ancona
  - Ancona, Marche/Ancona, Italy, 60126
    - Recruiting
    - A O Universitaria Ospedali Riuniti Ancona
    - Contact:
      
      Fabio Vagnarelli, MD
      
      Phone Number: +39 0715965705
      
      Email: f.vagnarelli@gmail.com
  - Ancona, Marche/Ancona, Italy, 60126
    - Not yet recruiting
    - Clinica cardiologica AZ ospedaliera Torrette
    - Contact:
      
      Federico Guerra, MD
      
      Phone Number: +390715965340
      
      Email: f.guerra@univpm.it
- Piemonte/Ivrea
  - Ivrea, Piemonte/Ivrea, Italy, 10015
    - Not yet recruiting
    - Ospedale Ivrea
    - Contact:
      
      Walter Grosso Marra, MD
      
      Phone Number: +39 0125 4141
      
      Email: grossomarra@yahoo.it
    - Contact:
      
      Margherita Cannillo
      
      Email: margheritacannillo@gmail.com
- Piemonte/Novara
  - Novara, Piemonte/Novara, Italy, 28100
    - Not yet recruiting
    - Ospedale Maggiore della Carità
    - Contact:
      
      Giuseppe Patti, MD
      
      Phone Number: +39 0321.3731
      
      Email: giuseppe.patti@maggioreosp.novara.it
- Piemonte/Torino
  - Torino, Piemonte/Torino, Italy, 10134
    - Recruiting
    - Molinette
    - Contact:
      
      Claudia Raineri, MD
      
      Phone Number: +393383285351
      
      Email: cloud.raineri@gmail.com
  - Torino, Piemonte/Torino, Italy, 10134
    - Not yet recruiting
    - Ospedale Koelliker di Torino
    - Contact:
      
      Paola Lusardi, MD
      
      Phone Number: 800-000-500
      
      Email: lusardi.paola@gmail.com
- Puglia/Bari
  - Bari, Puglia/Bari, Italy, 70124
    - Recruiting
    - Policlinico Bari
    - Contact:
      
      Cinzia Forleo, MD
      
      Phone Number: +39 080 5592678
      
      Email: cinzia.forleo@uniba.it
- Puglia/Foggia
  - Foggia, Puglia/Foggia, Italy, 71122
    - Not yet recruiting
    - A O Universitaria Ospedali Riuniti di Foggia
    - Contact:
      
      Natale Brunetti, MD
      
      Phone Number: +39 3287660350
      
      Email: natale.brunetti@unifg.it
  - Manfredonia, Puglia/Foggia, Italy, 71043
    - Not yet recruiting
    - Ospedale Casa Sollievo della Sofferenza
    - Contact:
      
      Giuseppe Di Stolfo, MD
      
      Phone Number: +390882410111
      
      Email: giuseppedistolfo@yahoo.it
- Puglia/Lecce
  - Lecce, Puglia/Lecce, Italy, 73100
    - Not yet recruiting
    - Ospedale Vito Fazzi
    - Contact:
      
      Stefania Marazia, MD
      
      Phone Number: +39 0832661111
      
      Email: stefaniamarazia@virgilio.it
- Puglia/Taranto
  - Taranto, Puglia/Taranto, Italy, 74010
    - Recruiting
    - Ospedale SS.ma Annunziata
    - Contact:
      
      Simona Rosania, MD
      
      Phone Number: +39 3294389789
      
      Email: simonarosania@alice.it
- Sardegna/Cagliari
  - Cagliari, Sardegna/Cagliari, Italy, 09121
    - Not yet recruiting
    - Azienda Ospedaliera G. Brotzu
    - Contact:
      
      Laura Cassisa, MD
      
      Phone Number: +39 070 5391
      
      Email: lacassisa@yahoo.it
    - Contact:
      
      Daniele Pasqualucci, MD
      
      Email: pasqualucci.daniele@gmail.com
  - Cagliari, Sardegna/Cagliari, Italy, 09124
    - Not yet recruiting
    - Azienda Ospedaliera Universitaria
    - Contact:
      
      Stefania Piga, MD
      
      Phone Number: +393407231433
      
      Email: stefania.piga74@gmail.com
- Sicilia/Catania
  - Catania, Sicilia/Catania, Italy, 95123
    - Recruiting
    - Policlinico Rodolico
    - Contact:
      
      Ines Monte, MD
      
      Phone Number: +39 3397345501
      
      Email: ines.monte@unict.it
- Sicilia/Messina
  - Messina, Sicilia/Messina, Italy, 98125
    - Not yet recruiting
    - Policlinico G. Martino
    - Contact:
      
      Gianluca Di Bella, MD
      
      Phone Number: +39 090 221 1
      
      Email: gdibella@unime.it
- Sicilia/Palermo
  - Palermo, Sicilia/Palermo, Italy, 90127
    - Not yet recruiting
    - Policlinico P. Giaccone
    - Contact:
      
      Giuseppina Novo, MD
      
      Phone Number: +39 091 2776161
      
      Email: giuseppina.novo@gmail.com
- Toscana/Arezzo
  - Arezzo, Toscana/Arezzo, Italy, 52100
    - Not yet recruiting
    - Ospedale San Donato
    - Contact:
      
      Maurizio Pieroni, MD
      
      Phone Number: +3905752551
      
      Email: mauriziopieroni@yahoo.com
- Toscana/Firenze
  - Firenze, Toscana/Firenze, Italy, 50139
    - Recruiting
    - Azienda Ospedaliero Universitaria Careggi e Meyer
    - Contact:
      
      Jacopo Olivotto, MD
      
      Phone Number: +393333314844
      
      Email: iacopo.olivotto@unifi.it
    - Contact:
      
      Francesco Cappelli, MD
      
      Phone Number: +393382504484
      
      Email: cappellif@aou-careggi.toscana.it
- Toscana/Pisa
  - Pisa, Toscana/Pisa, Italy, 56126
    - Recruiting
    - Fondazione Toscana Gabriele Monasterio
    - Contact:
      
      Andrea Barison, MD
      
      Phone Number: +393391584389
      
      Email: dr.andrea.barison@gmail.com
- Toscana/Siena
  - Siena, Toscana/Siena, Italy, 53100
    - Not yet recruiting
    - Azienda Ospedaliera Universitaria Siena
    - Contact:
      
      Matteo Cameli, MD
      
      Phone Number: +390577585518
      
      Email: matteo.cameli@unisi.it
    - Contact:
      
      Email: focardim@unisi.it
- Trentino Alto Adige/Trento
  - Trento, Trentino Alto Adige/Trento, Italy, 38123
    - Not yet recruiting
    - Ospedale S.Chiara
    - Contact:
      
      Michele Moretti, MD
      
      Phone Number: +393381772525
      
      Email: michele.moretti@apss.tn.it
- Triesta
  - Trieste, Triesta, Italy, 34170
    - Not yet recruiting
    - Azienda sanitaria universitaria Giuliano Isontina
    - Contact:
      
      Marco Merlo, MD
      
      Phone Number: +390403994865
      
      Email: Marco.merlo@asugi.sanita.fvg.it
- Umbria/Perugia
  - Perugia, Umbria/Perugia, Italy, 06129
    - Recruiting
    - Ospedale di Perugia
    - Contact:
      
      Cinzia Zuchi, MD
      
      Phone Number: +390755781
      
      Email: cinzia.zuchi80@gmail.com
- Veneto/Padova
  - Padova, Veneto/Padova, Italy, 35128
    - Recruiting
    - Ospedale Padova
    - Contact:
      
      Martina Petrazzolo Marra, MD
      
      Phone Number: +390498211111
      
      Email: martina.perazzolomarra@aopd.veneto.it
- Veneto/Verona
  - Verona, Veneto/Verona, Italy, 37126
    - Not yet recruiting
    - Ospedale Policlinico Sede di Borgo Roma
    - Contact:
      
      Anna Piccoli, MD
      
      Phone Number: +390458121111
      
      Email: anna.piccoli@univr.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

All patients affected by AFD, diagnosed according to current international guidelines, will be included in the study, after obtaining free and informed consent. The study plans, based on the estimated prevalence of the disease, to enroll approximately 800 patients over the course of 10 years.

Description

Inclusion Criteria:

Patients diagnosed with Anderson Fabry disease
Age ≥ 2 years at diagnosis
Obtaining informed consent from the patient and parent or legal guardian.

Exclusion Criteria:

- None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Definition of Fabry disease natural history Time Frame: From enrollment to mean follow-up of 5 years.	Prevalence of Fabry disease: number of diagnosed cases of Fabry disease per 100,000 individuals in the general population. Incidence of Fabry disease: number of new cases of Fabry disease per year per 100,000 individuals in the general population. Number of patients with morbidity (heart failure, arrhythmias, kidney failure, stroke) and mortality (cardiac and non cardiac death) events recorded during follow-up.	From enrollment to mean follow-up of 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fabry disease cardiac risk stratification Time Frame: From enrollment to mean follow-up of 5 years.	To identify clinical and instrumental predictors of morbidity and cardiovascular mortality, in order to enhance risk stratification of events and to personalize the most appropriate management plan for each patient.	From enrollment to mean follow-up of 5 years.
Correlation between genotype and cardiac involvement (ECG changes, LVH, T1/T2 mapping)/cardiac events. Time Frame: From enrollment to mean follow-up of 5 years.	To assess the correlation between genetic results (missense vs non-missense variants), phenotype (ECG abnormalities, degree of LVH by echo/CMR; T1 and T2 mapping values by CMR; amount of scar [LGE] by CMR) ), and prognosis (mortality/morbidity), with particular focus on differences in cardiac involvement between classic and late-onset forms with cardiac involvement.	From enrollment to mean follow-up of 5 years.
Identification of biomarkers for early diagnosis in Fabry disease Time Frame: From enrollment to mean follow-up of 5 years.	To investigate serological/tissue markers (troponin [ng/L], BNP [pg/L], microRNA [copies/ml]] and instrumental indicators (vacuolization by histology, T1 an T2 values by CMR) of early cardiac damage.	From enrollment to mean follow-up of 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

Principal Investigator: Elena Biagini, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2022

Primary Completion (Estimated)

January 31, 2031

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

January 9, 2025

First Submitted That Met QC Criteria

January 28, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)