Cerebral Creatine Deficiency Syndromes: Clinical Aspects, Treatment and Pathophysiology

  • Sylvia Stockler
  • Peter W. Schutz
  • Gajja S. Salomons
Part of the Subcellular Biochemistry book series (SCBI, volume 46)


Cerebral creatine deficiency syndromes (CCDSs) are a group of inborn errors of creatine metabolism comprising two autosomal recessive disorders that affect the biosynthesis of creatine – i.e. arginine:glycine amidinotransferase deficiency (AGAT; MIM 602360) and guanidinoacetate methyltransferase deficiency (GAMT; MIM 601240) – and an X-linked defect that affects the creatine transporter, SLC6A8 deficiency (SLC6A8; MIM 300036). The biochemical hallmarks of these disorders include cerebral creatine deficiency as detected in vivo by 1H magnetic resonance spectroscopy (MRS) of the brain, and specific disturbances in metabolites of creatine metabolism in body fluids. In urine and plasma, abnormal guanidinoacetic acid (GAA) levels are found in AGAT deficiency (reduced GAA) and in GAMT deficiency (increased GAA). In urine of males with SLC6A8 deficiency, an increased creatine/creatinine ratio is detected. The common clinical presentation in CCDS includes mental retardation, expressive speech and language delay, autistic like behaviour and epilepsy. Treatment of the creatine biosynthesis defects has yielded clinical improvement, while for creatine transporter deficiency, successful treatment strategies still need to be discovered. CCDSs may be responsible for a considerable fraction of children and adults affected with mental retardation of unknown etiology. Thus, screening for this group of disorders should be included in the differential diagnosis of this population. In this review, also the importance of CCDSs for the unravelling of the (patho)physiology of cerebral creatine metabolism is discussed


Creatine Monohydrate Creatine Transporter Creatine Synthesis Guanidino Compound GAMT Deficiency 
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Copyright information

© Springer 2007

Authors and Affiliations

  • Sylvia Stockler
    • 1
  • Peter W. Schutz
    • 2
  • Gajja S. Salomons
    • 3
  1. 1.Department of Pediatrics, Division of Biochemical Diseases, British Columbia Children’s HospitalUniversity of British ColumbiaVancouverCanada
  2. 2.Departments of Pediatrics, Pathology and Laboratory Medicine, Division of Biochemical DiseasesUniversity of British Columbia, British Columbia Children’s HospitalVancouverCanada
  3. 3.Department of Clinical Chemistry, Metabolic UnitVU University Medical CenterAmsterdamThe Netherlands

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