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Pediatr Neurol. 2015 Oct;53(4):360-363.e2. doi: 10.1016/j.pediatrneurol.2015.05.006. Epub 2015 May 16.

Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

Author information

1
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.
2
Division of Pediatric Neurology, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
3
Division of Biochemical Diseases (TIDE-BC), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
4
Department of Radiology, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
5
Department of Psychology, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
6
Child and Family Research Institute, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
7
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.
8
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.

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.

DISCUSSION:

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.

KEYWORDS:

Cerebral creatine deficiency; MR spectroscopy; behavior; global developmental delay; personalized medicine; seizures; speech; therapy

[Indexed for MEDLINE]

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