Creatine transporter defect
| Creatine transporter defect | |
|---|---|
 | |
| Classification and external resources | |
| OMIM | 300352 |
| DiseasesDB | 34691 |
| GeneReviews | |
Creatine transporter defect (CTD) is an X-linked disorder of creatine metabolism caused by defective transport of creatine into the brain. The condition was initially described in reports in 2001. Hemizygous males with this condition show intellectual disability, speech delay, seizures, and behavioural abnormalities. Heterozygous females can have varying symptoms. CTD is caused by mutations in the SLC6A8 gene, located at the Xq28 (short arm of the 'sex' chromosome). Clinically, it resembles the two other forms of cerebral creatine deficiencies (CCD's):
- L-arginine:glycine amidinotransferase deficiency, and
- guanidinoacetate methyltransferase deficiency.[1]
Diagnosis
The diagnosis of CTD is usually suspected based on the clinical presentation. A family history of X-linked intellectual disability, developmental coordination disorder and seizures is strongly suggestive.[2] The initial screening test is typically a measurement of urine creatine and creatinine. A ratio of creatine:creatinine of greater than 1.5 is suggestive of CTD. Biochemical screening tests are not always informative in heterozygous females.[3] Proton magnetic resonance spectroscopy will typically reveal the absence of a creatine peak, although this finding is shared amongst all cerebral creatine deficiencies. Follow-up testing can include genetic testing, such as sequencing, of SLC6A8.[1]
Treatment
CTD is difficult to treat because the defective transporter means creatine cannot reach the brain and other affected tissues, particularly in males. Some females with residual activity show benefit from creatine supplementation.[3]
Genetics
CTD is caused by mutations in SLC6A8 and inherited in an X-linked recessive manner. Hemizygous males will usually be severely affected, while female carriers can have varying symptoms - from unaffected to a similar presentation as an affected male.[1]
References
- 1 2 3 "#300352 - Cerebral Creatine Deficiency Syndrome 1". Johns Hopkins. Retrieved 2013-11-16.
- ↑ Leuzzi, V.; Mastrangelo, M.; Battini, R.; Cioni, G. (2013). "Inborn errors of creatine metabolism and epilepsy". Epilepsia 54 (2): 217–227. doi:10.1111/epi.12020. PMID 23157605.
- 1 2 Mercimek-Mahmutoglu, S.; Stöckler-Ipsiroglu, S.; Salomons, G. S.; Pagon, R. A.; Adam, M. P.; Bird, T. D.; Dolan, C. R.; Fong, C. T.; Stephens, K. (1993). "Creatine Deficiency Syndromes". PMID 20301745.