Progressive intestinal, neurological and psychiatric problems in two adult males with cerebral creatine deficiency caused by an SLC6A8 mutation.

Clinical Genetics (Impact Factor: 3.65). 11/2005; 68(4):379-81. DOI: 10.1111/j.1399-0004.2005.00489.x
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    ABSTRACT: Creatine is a naturally occurring metabolite that is synthesized endogenously and absorbed from the diet. This chapter explores the biochemistry of creatine, its role in the creatine kinase/phosphocreatine energy shuttle and support of buffering, transport, and regulation of cellular energetics. Dysfunctional brain creatine metabolism occurs in creatine deficiency syndromes and other neurological disorders outlined in this chapter. The therapeutic potential of creatine supplementation to improve neural energy metabolism and the role of MRS in examining creatine energetics are discussed.
    Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications, 1 edited by C. J. Stagg, D. L. Rothman, 12/2013: chapter 2.2: pages 91-103; Academic Press., ISBN: 978-0-12-401688-0
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    ABSTRACT: Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The condition mainly affects the brain while other creatine requiring organs, such as the muscles, are relatively spared. Recent studies have provided strong evidence that creatine synthesis also occurs in the brain, leading to the intriguing question of why cerebral creatine is deficient in creatine transporter deficiency. The possible mechanisms explaining the cerebral creatine deficiency are discussed. The creatine transporter knockout mouse provides a good model to study the disease. Over the past years several treatment options have been explored but no treatment has been proven effective. Understanding the pathogenesis of creatine transporter deficiency is of paramount importance in the development of an effective treatment.
    Journal of Inherited Metabolic Disease 05/2014; 37(5). · 4.14 Impact Factor
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    ABSTRACT: Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352). CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT (-/y) murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.
    F1000Research. 01/2014; 3:228.