title: [Cerebral creatine deficiency: first Spanish patients harbouring mutations in GAMT gene].
abstract: OBJECTIVE
  Brain creatine (Cr) deficiencies are a group of inborn errors of metabolism that are characterized by an absence or severe reduction of brain Cr. Clinically, these patients can display psychomotor/mental retardation and language disorders, commonly associated with epilepsy or movement disorders. Three metabolic defects are known: two affect synthesis - guanidinoacetate metiltransferase (GAMT) and glycine amidinotransferase (AGAT) deficiencies- and one affect the Cr transporter (CRTR). We present the first three Spanish patients with GAMT deficiency, and we compare their clinical phenotype and treatment response with other published cases.
  
  
  METHODS
  The three patients presented mental retardation, epilepsy and autistic behaviour. Patient 1 also had severe chorea. Diagnosis was done by biochemical and genetic procedures (guanidinoacetate quantification, determination of GAMT activity and mutation analysis in the GAMT gene).
  
  
  RESULTS
  An increase of guanidinoacetate was detected in urine and plasma. Brain magnetic resonance spectroscopy revealed low Cr levels. Enzymatic studies revealed a decreased GAMT activity in fibroblasts. Molecular analysis detected pathogenic mutations in the GAMT gene. After the deficiency was confirmed, the patients started treatment with Cr. In addition, patient 2 and 3 received an arginine-restricted diet and ornithine supplements. All them showed a partial improvement.
  
  
  CONCLUSIONS
  Patients with GAMT deficiency have an unspecific but relatively constant clinical presentation. Brain Cr deficiency should be considered in patients with mental retardation of unknown aetiology, specially in those with movement disorders or epilepsy. Early diagnosis is important in cases with known treatment such as GAMT deficiency.
authors.affiliation: Neuropediatría, Hospital Sant Joan de Déu y Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Esplugues de Llobregat, Barcelona, España.
authors.forename: Angela
authors.initials: A
authors.lastname: Sempere
authors.forename: Carmen
authors.initials: C
authors.lastname: Fons
authors.forename: Angela
authors.initials: A
authors.lastname: Arias
authors.forename: Pilar
authors.initials: P
authors.lastname: Rodríguez-Pombo
authors.forename: Begoña
authors.initials: B
authors.lastname: Merinero
authors.forename: Patricia
authors.initials: P
authors.lastname: Alcaide
authors.forename: Antoni
authors.initials: A
authors.lastname: Capdevila
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
authors.forename: Rosario
authors.initials: R
authors.lastname: Duque
authors.forename: Jesús
authors.initials: J
authors.lastname: Eirís
authors.forename: Pilar
authors.initials: P
authors.lastname: Poo
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernández-Alvarez
authors.forename: Jaume
authors.initials: J
authors.lastname: Campistol
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
mesh_terms: D000293:Adolescent; D001928:Brain Diseases, Metabolic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D003401:Creatine / Q000172:deficiency*; D005260:Female; D050937:Guanidinoacetate N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013030:Spain
chemical_list: C494506:GAMT protein, human; D050937:Guanidinoacetate N-Methyltransferase; D003401:Creatine