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

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• 作者：Sravan Jaggumantri ; B.Tech^a ; ^b ; Mary Dunbar ; MD^c ; Vanessa Edgar^a ; Cristina Mignone ; MD^d ; Theresa Newlove ; MS^e ; Rajavel Elango ; PhD^b ; ^f ; Jean Paul Collet ; MD ; PhD^b ; ^f ; Michael Sargent ; MD^d ; Sylvia Stockler-Ipsiroglu ; MD ; PhD^a ; ^f ; Clara D.M. van Karnebeek ; MD ; PhD^a ; ^b ; ^f ; ^g ; ^{cvankarnebeek@cw.bc.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cerebral creatine deficiency ; therapy ; personalized medicine ; behavior ; MR spectroscopy ; speech ; global developmental delay ; seizures
• 刊名：Pediatric Neurology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：53
• 期：4
• 页码：360-363.e2
• 全文大小：330 K

文摘

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.

d="absSec_2">Methods

d="abspara0015">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.

d="absSec_3">Results

d="abspara0020">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.

d="absSec_4">Discussion

d="abspara0025">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.