The diagnosis of CTD is usually suspected based on the clinical presentation of intellectual disability, abnormalities in cognitive and expressive speech, and developmental delay. Furthermore, a family history of X-linked intellectual disability, developmental coordination disorder, and seizures is strongly suggestive. Initial screening of CTD involves obtaining a urine sample and measuring the ratio of<unk>  to<unk> ne. If the ratio of<unk>  to<unk> ne is greater than 1.5, then the presence of CTD is highly likely. This is because a large ratio indicates a high amount of<unk>  in the urine. This, in turn, indicates inadequate transport of<unk>  into the brain and muscle. However, the urine screening test often fails in diagnosing heterozygous females. Studies have demonstrated that as a group heterozygous females have significantly decreased cerebral<unk>  concentration, but that individual heterozygous females often have normal<unk>  concentrations found in their urine. Therefore, urine screening tests are unreliable as a standard test for diagnosing CTD, particularly in females. A more reliable and sophisticated manner of testing for cerebral<unk>  concentrations is through in vivo proton magnetic resonance spectroscopy (1H MRS). In vivo 1H MRS uses proton signals to determine the concentration of specific metabolites. This method of testing is more reliable because it provides a fairly accurate measurement of the amount of<unk>  inside the brain. Similar to urine testing, a drawback of using 1H MRS as a test for CTD is that the results of the test could be attributed to any of the cerebral<unk>  deficiencies. The most accurate and reliable method of testing for CTD is through DNA sequence analysis of SLC6A8. DNA analysis of SLC6A8 allows the identification of the location and type of variant causing the cerebral<unk>  deficiency. Furthermore, DNA analysis of SLC6A8 is able to prove that a cerebral<unk>  deficiency is due to CTD and not GAMT or AGAT deficiency.
Creatine transporter defect
N-Acetylglutamate synthase deficiency
Cerebral creatine deficiency
Mitochondrial complex II deficiency
Lysosomal storage disease
D-bifunctional protein deficiency
Mitochondrial trifunctional protein deficiency
Trinucleotide repeat disorder