Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02298634 |
| Other study ID # |
BFD 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Withdrawn |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 spectrometry-based biomarker for the early and sensitive diagnosis
of Farber disease from the blood
Description:
Farber disease (FD), also known as Farber's lipogranulomatosis, is an autosomal recessive
lysosomal storage disease marked by a deficiency in enzyme ceramidase which causes a
progressive accumulation of fatty material lipids leading to abnormalities in the joints,
liver, throat, tissues and central nervous system.
FD is an extremely rare disorder, with a prevalence of less than 1/1000000. Currently only
about 80 cases are reported worldwide. Disease onset is typically in early infancy but may
occur later in life.
FD is caused by a mutation in the ASAH1 gene, situated on the short arm of chromosome 8. This
gene codes for acid ceramidase, a lysosomal heterodimeric enzyme that hydrolyzes ceramide
into sphingosine and fatty acid. To date, less than 25 distinct mutations have been
identified in Farber patients, but no large deletions have yet been reported. It is inherited
with an autosomal recessive pattern.
The clinical presentation of FD is characterized by the appearance of subcutaneous skin
nodules, ordinarily near the joints, most often interphalangeal, wrist, elbow and ankle
joints, or over points of mechanical pressure. These manifestations are very painful and lead
to progressive joint stiffness, limitation of motion by contractures and finally to
immobilization and deformation of joints. Also, a characteristic sign of FD is the
development of a progressive hoarseness due to laryngeal involvement.
Beside these major manifestations seven phenotypes have been described which differ in
severity and additional organ involvement, like the lungs, nervous system, heart and lymph
nodes. Dependent on residual lysosomal ceramidase turnover, patients have a variable degree
of central nervous system disease, leading to progressive neurologic deterioration. In most
cases the neuronal dysfunction rather than the general physical dystrophy seems to limit the
duration of FD. As well, patients with FD may die due to pulmonary disease with interstitial
pneumonia.
First symptoms usually appear between the newborn period and the first birthday. Milder forms
of type 3 were described with onset at 20 months of age. Clinical manifestation in type 5 of
FD, dominated by neurologic deterioration, begins at 1 to 2 1/2 years of life. Patients
mainly die within the first years of life, but prolonged courses in patients without severe
nervous disease may also be observed.
Type 1 is the most common or classical form of this condition and is associated with the
classic signs of voice, skin, and joint problems that begin a few months after birth.
Developmental delay and lung disease also commonly occur. Infants born with type 1 FD usually
survive only into early childhood.
Types 2 and 3 generally have less severe signs and symptoms than the other types. Affected
individuals have the three classic signs and usually do not have developmental delay.
Children with these types of FD typically live into mid- to late childhood.
Types 4 and 5 are associated with severe neurological problems. Type 4 usually causes
life-threatening health problems beginning in infancy due to massive lipid deposits in the
liver, spleen, lungs, and immune system tissues. Children with this type typically do not
survive past their first year of life. Type 5 is characterized by progressive decline in
brain and spinal cord (central nervous system) function, which causes paralysis of the arms
and legs (quadriplegia), seizures, loss of speech, involuntary muscle jerks (myoclonus), and
developmental delay. Children with type 5 FD survive into early childhood.
Types 6 and 7 are very rare, and affected individuals have other associated disorders in
addition to FD.
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.
