Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02778295 |
| Other study ID # |
BFA 06-2018 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 20, 2018 |
| Est. completion date |
February 28, 2021 |
Study information
| Verified date |
February 2023 |
| Source |
CENTOGENE GmbH Rostock |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Development of a new mass spectrography-based biomarker for the early and sensitive diagnosis
of Fabry disease from the blood
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.
