Cerebral Creatine Deficiency Disorders

Cerebral creatine deficiency disorders that result in very low levels of creatine in the brain, can cause in intellectual disability, seizures, expressive speech disorder and behavior disorders if not treated in early childhood. CCDDs comprise disorders of creatine synthesis (arginine:glycine [AGAT; MIM 602360]; guanidinoacetate methyltransferase deficiency [GAMT; MIM 601240]) and of creatine transport (SLC6A8 deficiency [SLC6A8; MIM 300036]). Inborn errors of creatine synthesis-but not, as yet, of transport-can be treated by creatine substitution and are thus treatable causes of intellectual disability.