title: GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis.
abstract: BACKGROUND
  Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients.
  
  
  METHODS
  The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation.
  
  
  RESULTS
  Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged.
  
  
  CONCLUSIONS
  Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.
authors.affiliation: Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
authors.forename: S
authors.initials: S
authors.lastname: Stoeckler-Ipsiroglu
authors.forename: A
authors.initials: A
authors.lastname: Adami
authors.forename: R
authors.initials: R
authors.lastname: Appleton
authors.forename: H Caldeira
authors.initials: HC
authors.lastname: Araújo
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: R
authors.initials: R
authors.lastname: Ensenauer
authors.forename: E
authors.initials: E
authors.lastname: Fernandez-Alvarez
authors.forename: P
authors.initials: P
authors.lastname: Garcia
authors.forename: C
authors.initials: C
authors.lastname: Grolik
authors.forename: C B
authors.initials: CB
authors.lastname: Item
authors.forename: V
authors.initials: V
authors.lastname: Leuzzi
authors.forename: I
authors.initials: I
authors.lastname: Marquardt
authors.forename: A
authors.initials: A
authors.lastname: Mühl
authors.forename: R A
authors.initials: RA
authors.lastname: Saelke-Kellermann
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: R
authors.initials: R
authors.lastname: Surtees
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: R
authors.initials: R
authors.lastname: Vasconcelos
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: L
authors.initials: L
authors.lastname: Vilarinho
authors.forename: E
authors.initials: E
authors.lastname: Wilichowski
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003401:Creatine / Q000378:metabolism*; D004827:Epilepsy / Q000209:etiology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D050937:Guanidinoacetate N-Methyltransferase / Q000172:deficiency*; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000503:physiopathology*; D009069:Movement Disorders / Q000209:etiology
chemical_list: D050937:Guanidinoacetate N-Methyltransferase; C004946:glycocyamine; D003401:Creatine; D005998:Glycine