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Biomarker for Patients With Fabry Disease (BioFabry) (BioFabry)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02778295
Recruitment Status : Active, not recruiting
First Posted : May 19, 2016
Last Update Posted : May 13, 2021
Information provided by (Responsible Party):

Brief Summary:
Development of a new mass spectrography-based biomarker for the early and sensitive diagnosis of Fabry disease from the blood

Condition or disease
Angiokeratomas Chronic Kidney Disease Ocular Abnormalities Hearing Loss

Detailed Description:

Fabry disease is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.

Annual incidence is reported to be 1 in 80,000 live births but this figure may underestimate disease prevalence. When late-onset variants of the disease are considered, a prevalence of approximately 1 in 3,000 has been suggested. Fabry disease is pan-ethnic.

Fabry disease is a disorder of glycosphingolipid metabolism caused by deficient or absent lysosomal alpha-galactosidase A activity related to mutations in the GLA gene (Xq21.3-q22) encoding the alpha-galactosidase A enzyme. Deficient activity results in accumulation of globotriaosylceramide (Gb3) within lysosomes, believed to trigger a cascade of cellular events.

Fabry disease is transmitted as an X-linked trait. The existence of atypical, late-onset, variants and the availability of specific therapy complicate genetic counseling.

The clinical picture covers a wide spectrum ranging from mild cases in heterozygous females, to severe cases in classically affected hemizygous males with no residual alpha-galactosidase A activity. These patients may have all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular (hearing loss and vertigo) and cerebrovascular (transient ischemic attacks, strokes) symptoms of the disease.

Female patients may have very mild to severe symptoms. Pain is a common early symptom of Fabry disease (chronic pain characterized by burning and tingling paresthesia and occasional episodic crises characterized by agonizing burning pain). Pain may resolve in adulthood.

Anhidrosis or hypohidrosis may occur causing heat and exercise intolerance. Other signs include corneal changes ("cornea verticilata"), Definitive laboratory diagnosis involves demonstration of marked enzyme deficiency in hemizygous males. Enzyme analysis may occasionally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation, making molecular testing (genotyping) of females mandatory.

With age, progressive damage to vital organ systems develops, possibly leading to organ failure. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit the life-expectancy .

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Patients with Fabry disease or high-grade suspicion for Fabry disease

Primary Outcome Measures :
  1. Sequencing of the Fabry disease related gene [ Time Frame: 4 weeks ]
    Next-Generation Sequencing (NGS) of the GLA gene will be performed. The mutation will be confirmed by Sanger sequencing.

Secondary Outcome Measures :
  1. The Fabry disease specific biomarker candidates finding [ Time Frame: 24 months ]
    The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.

Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of Mass-spectrometry, a blood sample will be taken via using a dry blood spot filter card. To proof the correct Fab-ry diagnosis in those patients where up to the enrollment in the study no genetic testing has been done, sequencing of Fabry disease will be done.The analyses will done at:

Centogene AG Am Strande 7 18055 Rostock Germany

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Fabry disease or high-grade suspicion for Fabry disease


  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients of both genders older than 2 months
  • The patient has a diagnosis of Fabry disease or a high-grade suspicion for Fabry disease
  • High-grade suspicion present, if one or more inclusion criteria are valid:

    • Positive family anamnesis for Fabry disease
    • Pin and burning in the hands and feet
    • Angiokeratomas
    • Gastrointestinal problems
    • Heart problems
    • Kidney problems


  • No Informed consent from the patient or the parents before any study related procedures.
  • Patients of both gender younger than 2 months
  • No diagnosis of Fabry disease or no valid criteria for profound suspicion of Fabry disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02778295

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Centogene GmbH
Rostock, Germany, 18055
NIRMAN-University of Mumbai-Institute of Research in Mental and Neurological handicap
Mumbai, India, 400705
Sri Lanka
Lady Ridgeway Hospital for Children
Colombo 8, Sri Lanka, 00800c
Sponsors and Collaborators
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Study Chair: Peter Bauer, Prof. Centogene GmbH
Additional Information:
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Responsible Party: CENTOGENE GmbH Rostock Identifier: NCT02778295    
Other Study ID Numbers: BFA 06-2018
First Posted: May 19, 2016    Key Record Dates
Last Update Posted: May 13, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CENTOGENE GmbH Rostock:
Fabry Disease
Additional relevant MeSH terms:
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Hearing Loss
Fabry Disease
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases