Creatine deficiency syndromes and the importance of creatine synthesis in the brain

@article{Braissant2011CreatineDS,
  title={Creatine deficiency syndromes and the importance of creatine synthesis in the brain},
  author={Olivier Braissant and Hugues Henry and Elidie B{\'e}ard and Jos{\'e}phine Uldry},
  journal={Amino Acids},
  year={2011},
  volume={40},
  pages={1315-1324}
}
Creatine deficiency syndromes, due to deficiencies in AGAT, GAMT (creatine synthesis pathway) or SLC6A8 (creatine transporter), lead to complete absence or very strong decrease of creatine in CNS as measured by magnetic resonance spectroscopy. Brain is the main organ affected in creatine-deficient patients, who show severe neurodevelopmental delay and present neurological symptoms in early infancy. AGAT- and GAMT-deficient patients can be treated by oral creatine supplementation which improves… Expand
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References

SHOWING 1-10 OF 101 REFERENCES
Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology.
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.Expand
AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: A review
TLDR
This review presents a comprehensive framework, including new hypotheses, on brain creatine metabolism and transport, both in normal conditions and in case of creatine deficiency, as well as a synthetic view on creatine and guanidinoacetate levels in the brain. Expand
Creatine Deficiency in the Brain: A New, Treatable Inborn Error of Metabolism
ABSTRACT: In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalizedExpand
Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect?
TLDR
Treatment with oral creatine monohydrate demonstrated no observable increase in brain creatine with proton MRS and no improvement in clinical symptoms, and a novel brain creatine deficiency syndrome most likely representing a creatine transporter defect is reported. Expand
Dissociation of AGAT, GAMT and SLC6A8 in CNS: Relevance to creatine deficiency syndromes
TLDR
The cell-to-cell co-expression of AGAT, GAMT and SLC6A8 in various regions of rat CNS showed that in most structures, cells co-expressing AGAT+GAMT (equipped for autonomous creatine synthesis) were in low proportions, and it was shown that brain cells take up guanidinoacetate and convert it to creatine. Expand
Creatine replacement therapy in guanidineoacetate methyltransferase deficiency, a novel inborn error of metabolism
TLDR
Long-term oral administration of creatine-monohydrate to an infant with extrapyramidal signs resulted in substantial clinical improvement, disappearance of magnetic resonance (MRI) signal abnormalities in the globus pallidus, and normalisation of slow background activity on the electroencephalogram (EEG). Expand
High frequency of creatine deficiency syndromes in patients with unexplained mental retardation
TLDR
A high frequency of CCDS in mentally retardation in mentally retarded children, mostly boys with an X-linked creatine transporter deficiency is reported, and diagnosis was further confirmed using brain proton MR spectroscopy and MRI. Expand
Lack of creatine in muscle and brain in an adult with GAMT deficiency
TLDR
Creatine substitution combined with a guanidinoacetate‐lowering diet introduced first at the age of 26 years was shown to be effective by an impressive improvement of epileptic seizures, mental capabilities, and general behavior and by normalization of the 31P spectrum in the skeletal muscle. Expand
Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency.
TLDR
In vitro data lend support to the idea of a certain passive transport of CEE in both pathological and control cells, although more lipophilic molecules or other cell systems that mimic the BBB should be used for a better approach to the in vivo system. Expand
Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism.
TLDR
A patient with this defect, a 4-year-old girl with a dystonic-dyskinetic syndrome in addition to developmental delay and therapy-resistant epilepsy, was described and treatment with orally administered creatine resulted in clinical improvement and an increase of creatine in cerebrospinal fluid and brain tissue. Expand
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