Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02934854 |
| Other study ID # |
BCDS 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Withdrawn |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 ear-ly and sensitive diagnosis
of the Creatine Deficiency Syndromes from dry-blood-spot sample
Description:
The Creatine Deficiency Syndromes (CDS) are a group of inborn errors of metabolism which
interrupt the biosynthesis or transportation of creatine. Individuals with CDS classically
present neurological symptoms (seizures, movement disorders and myopathy), and behavioral
manifestations. This group includes two creatine biosynthesis disorders (Guanidinoacetate
Methyltransferase Deficiency and L-Arginine: Glycine Amidinotransferase Deficiency), as well
as X-linked Creatine Transporter Deficiency.
Guanidinoacetate Methyltransferase Deficiency:
Guanidinoacetate Methyltransferase Deficiency is inherited in an autosomal recessive manner
and is caused by biallelic mutations in the GAMT gene. This gene maps to 19p13.3 and is
involved in the biosynthesis of creatine. Individuals with this deficiency typically present
with severe intellectual disabilities and seizure disorders which may be resistant to drug
therapy. Behavioral problems, including autistic behaviors and self-mutilation are common,
and pyramidal/extrapyramidal symptoms affect about one-half of patients. Dietary management
via manipulation of critical amino acids may improve clinical outcome. Mutations in the GAMT
gene are a relatively rare cause of creatine deficiency syndrome.
L-Arginine: Glycine Amidinotransferase Deficiency:
L-Arginine: Glycine Amidinotransferase Deficiency is a very rare type of CDS characterized by
global developmental delay, appearing in infancy, which can be associated with language
impairment and autistic behavior in some, as well as a mild to moderate intellectual
disability. Progressive muscle weakness and fatigability have been reported in older
patients. Seizures and failure to thrive have also been described. If creatine
supplementation is administered early enough, psychomotor delay may be avoided. This
deficiency is caused by mutations in GATM gene, located to chromosome 15q15.1. This gene
encodes the enzyme L-Arginine: Glycine Amidinotransferase, which converts arginine and
glycine to ornithine and guanidinoacetate in the creatine cycle pathway. This deficiency is
transmitted in an autosomal recessive manner.
X-linked Creatine Transporter Deficiency:
X-linked Creatine Transporter Deficiency is a creatine deficiency syndrome characterized
clinically by global developmental delay, intellectual disability with prominent
speech/language delay, autistic behavior and seizures. Affected individuals may present low
weight gain, muscular hypotonia, and poor muscle mass. Subtle dysmorphic features such as
midface hypoplasia, long face, and prominent chin have been reported in various affected male
patients. In adult patients, cardiac and gastrointestinal disorders have been reported. The
onset of symptoms occurs during infancy, usually before the age of 2 years. Males are mainly
affected, but females can also have various degrees of severity of disease manifestations.
This deficiency has been reported in more than 150 individuals worldwide and is mostly due to
frameshift and splicing mutations in the creatine transporter gene SLC6A8 (Xp28).
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.
