Reduced creatine levels in the brain and in body fluids/tissues are the common denominator of primary (AGAT, GAMT, X-linked creatine transporter (SLC6A8) deficiency) and secondary (OAT deficiency) creatine disorders. Developmental delay/intellectual disability, speech delay, and behavioral problems, combined with epilepsy, and movement disorders are characteristic clinical features of primary creatine deficiency syndromes. Chorioretinal degeneration is the clinical hallmark of OAT deficiency. Diagnostic markers include high (GAMT) or low (AGAT) levels of guanidinoacetate, a high urinary creatine excretion (SLC6A8 deficiency), and high plasma ornithine levels (OAT deficiency). Treatments comprise substitution of creatine (AGAT deficiency) combined with l-ornithine (GAMT deficiency) and arginine-restricted diet (GAMT and OAT deficiency). Administration of creatine and of substrates for intracerebral creatine synthesis (l-arginine and l-glycine) have limited therapeutic effects in CrT deficiency. Despite availability of causal treatments and improved outcomes after early recognition, creatine disorders are still under-recognized. All patients with unexplained developmental delay/intellectual disability should be screened for these disorders.
KeywordsIntellectual Disability Creatine Supplementation Creatine Monohydrate Creatine Transporter Creatine Synthesis
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