Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy (FABRY)

FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Indeed, recently, in addition with affected males FD developing a "classic" phenotype, " cardiac variant " and " renal variant " have been reported for FD patients with predominant or exclusive cardiac or renal involvement. " Neurologic variant " could exist.

Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy (acroparesthesias and pain).

Aims will be to determine the prevalence of Fabry disease in patients with stroke or small fiber neuropathy, and their characteristics

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Diagnostic test: Measurements of the alpha-GAL enzyme activity

Detailed Description

FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Indeed, recently, in addition with affected males FD developing a "classic" phenotype, " cardiac variant " and " renal variant " have been reported for FD patients with predominant or exclusive cardiac or renal involvement. " Neurologic variant " could exist.

Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy (acroparesthesias and pain).

1. Considering strokes, they are the third leading cause of death in France, with more than 140,000 people presenting a stroke per year. Stroke incidence is 1-2/1000 people per year. If the mean age of stroke patient is 72 yo, 25% of them are under 55 yo. The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of FD in people with cryptogenic ischaemic stroke are limited and controversial. In addition to cryptogenic strokes, FD can lead to stroke from arterial or heart diseases (secondary to high blood pressure, renal insufficiency, cardiomyopathy, rate variability, arrhythmias, valvular insufficiency).

   The investigators aimed to evaluate the frequency of FD in a cohort of stroke patients in tertiary stroke centers in consecutively recruited patients under 60 yo. The investigators will include patients with so-called cryptogenic stroke but also stroke patients due to large artery atherosclerosis, cardioembolism, and small-vessel occlusion. The investigators will also study the clinical and radiological characteristic of stroke patients due to FD, and will compare these data with those from patients without FD, supported by biochemical and genetic findings.

2. Considering peripheral nervous system, Small fiber neuropathy (SFN) is a subgroup of peripheral neuropathy which is characterized by an affection of the thin myelinated A-δ and unmyelinated C-fibers. SFN patients present with sensory symptoms and pain. SFN are not a rare condition; recent study showed a minimum prevalence of 50/100.000. The most commonly etiology reported for SFN is diabetes mellitus ; Other possible etiologies include connective tissue disease, celiac disease, thyroid dysfunction, vitamin B12 deficiency, monoclonal gammopathy, HIV and hepatitis C infections, amyloidosis, toxicity due to alcohol or drugs, and hereditary neuropathies including FD, suspected to be underdiagnosed.

In SFN patients,the investigators aimed to screen for FD in our tertiary national center for peripheral neuropathies, in addition to others diseases or affections, to evaluate the frequency of FD in a large cohort of SFN patients, and describe the clinical phenotype of SFN in FD patients compared to other ones.

• Study Type: Observational
• Enrollment (Actual): 379

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94270
    • CHU de Bicêtre, UNSIV (neurovascular stroke unit)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients between 18 and 60 years old diagnosed with a TIA/ strocke or a SFN

Description

Inclusion Criteria:

• patient over 18 yo and under 60 yo
• diagnosed with a TIA / stroke (ischemic and haemorrhagic strokes) based on clinical evaluation and MRI
• diagnosed with small fibers neuropathy (SFN) with normal nerve conduction studies in conventional electrophysiology

Exclusion Criteria:

• patients over 60 yo

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Molecular and genetic tests; Measurements of the alpha-GAL enzyme activity will be performed knowing that for male patients with alpha-GAL activities below the cut-off value and all female patients, a blood sampling for full genetic sequencing of all seven exons including promotors of the a-GAL gene will be done	Diagnostic test: Measurements of the alpha-GAL enzyme activity; Blotting paper blood tests in order to highlight an enzyme deficiency for hemizygous males with DBS kits in order to detect Fabry disease, with genetic confirmation if an abnormality is detected. For women genotyping is mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of FD in a cohort of stroke patients	number of patients with fabry disease in the cohort of stroke patients (1000 patients)	at the end of the study (an average of 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of FD in a cohort of Small fiber neuropathy (SFN) patients	number of patients with fabry disease in the cohort of small fiber neuropathy patients (100 patients)	at the end of the study (an average of 2 years)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Shire International GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2018
• Primary Completion (Actual): December 24, 2021
• Study Completion (Actual): December 24, 2021

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Stroke; Fabry; Cerebrovascular Accident; small fiber neuropathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Neuromuscular Diseases; Peripheral Nervous System Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Small Fiber Neuropathy
• Other Study ID Numbers: HAO16026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No