Creatine Deficiency Disorders

Abstract: Creatine deficiency disorders (CDDs)—comprising guanidinoacetate methyltransferase (GAMT) deficiency, L-arginine:glycine amidinotransferase (AGAT) deficiency, and creatine transporter (SLC6A8) deficiency (CRTR)—are a group of rare inherited metabolic conditions that disrupt cerebral energy homeostasis, leading to a spectrum of neurologic impairments. Disruptions in creatine synthesis or transport adversely affect high-energy–demand tissues, resulting in wide phenotypic variability that usually includes intellectual disability and behavioral abnormalities. Clinical presentations may also include speech-language disorder, autism spectrum behaviors, seizures, hypotonia, muscle weakness/myopathy, and extrapyramidal movement disorders. In the literature, there have been at least 130 reported patients with GAMT deficiency, 16 reported patients with AGAT deficiency, and 130 reported patients with CRTR.1 Despite the rarity of these conditions, recent advances in genetics and neuroimaging have refined our understanding of these disorders and underscored the critical importance of early intervention.

Link to article: https://www.neurology.org/doi/10.1212/WNL.0000000000213687

PubMed:  https://pubmed.ncbi.nlm.nih.gov/40397840/

Authors: Andrew Silverman

Key Terms: Multiple CCDS, Clinical Study, NBS, MRS, Diagnostic, Pediatric Patient, GAMT, AGAT, CTD