title: Guanidinoacetate methyltransferase (GAMT) deficiency: late  onset of movement disorder and preserved expressive language.
abstract: Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine biosynthesis, characterized by early-onset learning disability and epilepsy in most affected children. Severe expressive language delay is a constant feature even in the mildest clinical phenotypes.We report the clinical, biochemical, imaging, and treatment data of two female siblings (18y and 13y) with an unusual phenotype of GAMT deficiency. The oldest sibling had subacute onset of a movement disorder at age 17 years, later than has been previously reported. The younger sibling had better language skills than previously described in this disorder. After treatment with creatine, arginine restriction and ornithine-supplemented diet, seizure severity and movement disorder were reduced but cognition did not improve. This report confirms that GAMT deficiency, a heterogeneous, potentially treatable disorder, detected by increased levels of guanidinoacetate in body fluids (e.g. plasma or urine) or by an abnormal creatine peak on magnetic resonance spectroscopy, should be considered in patients of any age with unexplained, apparently static learning disability and epilepsy.
authors.affiliation: Department of Neurology, Children's University Hospital, Dublin, Ireland.
authors.forename: Declan J
authors.initials: DJ
authors.lastname: O'Rourke
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ryan
authors.forename: Gajja
authors.initials: G
authors.lastname: Salomons
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Ahmad
authors.initials: A
authors.lastname: Monavari
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001921:Brain / Q000473:pathology*; D003401:Creatine / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D050937:Guanidinoacetate N-Methyltransferase / Q000097:blood / Q000172:deficiency* / Q000652:urine; D006801:Humans; D007805:Language Development Disorders / Q000178:diet therapy* / Q000201:enzymology* / Q000473:pathology; D007859:Learning Disabilities / Q000178:diet therapy / Q000201:enzymology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009069:Movement Disorders / Q000178:diet therapy* / Q000201:enzymology* / Q000473:pathology; D009952:Ornithine / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014429:Twins, Dizygotic
chemical_list: D015415:Biomarkers; D003404:Creatinine; D009952:Ornithine; D050937:Guanidinoacetate N-Methyltransferase; D003401:Creatine