title: Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect.
abstract: BACKGROUND
  X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter (CTP) encoded by the SLC6A8 gene.
  
  
  METHODS
  We report here a series of six patients with severe CTP deficiency, four males and two females; clinical presentations include mild to severe mental retardation (6/6), associated with psychiatric symptoms (5/6: autistic behaviour, chronic hallucinatory psychosis), seizures (2/6) and muscular symptoms (2/4 males). Diagnosis was suspected upon elevated urinary creatine/creatinine (except in one of the female patients) and on a markedly decreased creatine peak on magnetic resonance spectroscopy (MRS). Diagnosis was confirmed by molecular analysis that identified four novel mutations not reported so far, including a mutation found twice in two male patients. All patients were treated successively and according to the same protocol by creatine alone then combined to its precursors, L-glycine and L-arginine for 42 months.
  
  
  CONCLUSIONS
  In our patients, creatine supplementation alone or with its precursors L-glycine and L-arginine showed benefit only in the muscular symptoms of the disease and no improvement in the cognitive and psychiatric manifestations and did not modify brain creatine content on MRS of male and female CTP deficient patients. New treatment strategies are required including creatine derivatives transported independently from CTP or using alternative pathways and transporters.
authors.affiliation: Reference Center for Inherited Metabolic Disorders (MaMEA), Necker-Enfants Malades Hospital, Paris Descartes University, 149 Rue de Sèvres, 75743 Paris Cedex, France. vassili.valaya@nck.aphp.fr
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Allel
authors.initials: A
authors.lastname: Chabli
authors.forename: Valerie
authors.initials: V
authors.lastname: Barbier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Anne
authors.initials: A
authors.lastname: Philippe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.forename: Michel
authors.initials: M
authors.lastname: Mazzuca
authors.forename: David
authors.initials: D
authors.lastname: Cheillan
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Yves
authors.initials: Y
authors.lastname: de Keyzer
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D020157:Amino Acid Transport Disorders, Inborn / Q000628:therapy*; D001120:Arginine / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis; D003401:Creatine / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000627:therapeutic use*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; C080679:creatine transporter; D001120:Arginine; D003401:Creatine; D005998:Glycine