title: Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.
abstract: BACKGROUND
  Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation.
  
  
  METHODS
  Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis.
  
  
  RESULTS
  Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making.
  
  
  CONCLUSIONS
  Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research.
authors.affiliation: Division of Biochemical Diseases (TIDE-BC), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Sravan
authors.initials: S
authors.lastname: Jaggumantri
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Dunbar
authors.affiliation: Division of Biochemical Diseases (TIDE-BC), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Edgar
authors.affiliation: Department of Radiology, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mignone
authors.affiliation: Department of Psychology, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Theresa
authors.initials: T
authors.lastname: Newlove
authors.affiliation: Child and Family Research Institute, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors.forename: Rajavel
authors.initials: R
authors.lastname: Elango
authors.affiliation: Child and Family Research Institute, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Collet
authors.affiliation: Department of Radiology, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Sargent
authors.affiliation: Division of Biochemical Diseases (TIDE-BC), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stockler-Ipsiroglu
authors.affiliation: Division of Biochemical Diseases (TIDE-BC), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada. Electronic address: cvankarnebeek@cw.bc.ca.
authors.forename: Clara D M
authors.initials: CD
authors.lastname: van Karnebeek
mesh_terms: D000284:Administration, Oral; D001120:Arginine / Q000008:administration & dosage*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D002648:Child; D003401:Creatine / Q000008:administration & dosage* / Q000172:deficiency*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005998:Glycine / Q000008:administration & dosage*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055118:Medication Adherence; D038901:X-Linked Intellectual Disability / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency*; D012436:S-Adenosylmethionine / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D002491:Central Nervous System Agents; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012436:S-Adenosylmethionine; D001120:Arginine; D003401:Creatine; D005998:Glycine
keywords: Cerebral creatine deficiency; MR spectroscopy; behavior; global developmental delay; personalized medicine; seizures; speech; therapy