Cerebral Creatine Deficiency Syndrome (CCDS) results from malfunctioning transportation of creatine or impaired creatine synthesis, resulting in creatine metabolism errors. There are three primary types of CCDS: creatine transporter deficiency (CTD), guanidinoacetate methyltransferase deficiency (GAMT), and agrinine: glycine amidinotransferase deficiency (AGAT).1 CTD is the most common form of CCDS and is resultant of a mutation in SLC6A8, the creatine transporter gene. Both GAMT and AGAT can be treated by creatine supplementation, but lack of a functioning transporter in the brain prevents creatine from entering neuronal cells.
In humans, the inheritance pattern for CTD is X-linked, meaning that it manifests in males due to it being located on the X chromsome. Female carriers of the disorder tend to not to exhibit overt symptoms of the disorder as they have two x chromosomes.
Lack of creatine in the brain has severe impacts on function due to creatine being necessary to recycle adenosine triphosphate (ATP) in the brain, that is essential in sustaining the dynamic energy requirements during brain development. Afflicted patients exhibit global developmental delays, and many present intellectual disability of varying severity. Additional symptoms of CCDS include gastrointestional issues, seizure disorders, behavior disorders, muscle weakness, and autism-like behaviors.
In order to study treatment methods for CTD, Zebrafish, Danio rerio, are being used as a model organism. Zebrafish have two paralogs of the slc6a8 gene: an ortholog, slc6a8a and its paralog, slc6a8b. A model organism for CTD in zebrafish would ideally have both copies of the gene knocked out. The purpose of this study was to identify slc6a8a knockout fish using genotyping.