Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect

The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we noticed an age-related decline in IQ subscales in boys affected with the CRTR defect.

• Publication year

  2011

• Venue

  Journal of Inherited Metabolic Disease

• Publication date

  2011-05-10

• Fields of study

  Medicine

• Identifiers
  DOI 10.1007/s10545-011-9345-1PMID 21556832PMCID 3249187
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• GeneReviews at GeneTests Medical Genetics Information Resource (Database Online)

  2012cited by this paper
• Inborn Metabolic Diseases: Diagnosis and Treatment

  2012cited by this paper
• Treatment of intractable epilepsy in a female with SLC6A8 deficiency.

  2010cited by this paper
• Dissociation of AGAT, GAMT and SLC6A8 in CNS: relevance to creatine deficiency syndromes.

  2010cited by this paper
• Na(+)/Cl(-)/creatine transporter activity and expression in rat brain synaptosomes.

  2010cited by this paper
• Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency.

  2010influential reference
• S-Adenosyl-l-methionine restores photoreceptor function following acute retinal ischemia

  2009influential reference
• Immunohistochemical localisation of the creatine transporter in the rat brain.

  2009cited by this paper
• Treatment with l-Arginine improves neuropsychological disorders in a child with Creatine transporter defect

  2008influential reference
• 1H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency

  2008cited by this paper
• AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: A review

  2008influential reference
• CARDIAC MANIFESTATIONS IN A CHILD WITH A NOVEL MUTATION IN CREATINE TRANSPORTER GENE SLC6A8

  2008cited by this paper
• Expression and possible role of creatine transporter in the brain and at the blood‐cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant

  2008cited by this paper
• Arginine and glycine stimulate creatine synthesis in creatine transporter 1-deficient lymphoblasts.

  2008cited by this paper
• Studies of age‐correlated features of cognitive‐behavioral development in children and adolescents with genetic disorders

  2007cited by this paper
• Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo.

  2007cited by this paper
• Expression and function of AGAT, GAMT and CT1 in the mammalian brain.

  2007cited by this paper
• Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application

  2007cited by this paper
• Exocytotic release of creatine in rat brain

  2006cited by this paper
• The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds.

  2006cited by this paper
• X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype

  2006cited by this paper
• X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism

  2006cited by this paper
• Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X‐linked mental retardation in two unrelated Dutch families

  2005cited by this paper
• 1H MR spectroscopy of the brain in Cr transporter defect.

  2005cited by this paper
• Progressive intestinal, neurological and psychiatric problems in two adult males with cerebral creatine deficiency caused by an SLC6A8 mutation

  2005cited by this paper
• Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport.

  2004cited by this paper
• Applied Longitudinal Analysis

  2004cited by this paper
• Creatine deficiency syndromes

  2003cited by this paper
• X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.

  2002cited by this paper
• Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?

  2002cited by this paper
• Congenital creatine transporter deficiency.

  2002cited by this paper
• X‐linked creatine deficiency syndrome: A novel mutation in creatine transporter gene SLC6A8

  2002cited by this paper
• Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study.

  2001influential reference
• X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.

  2001cited by this paper
• Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect?

  2001cited by this paper
• Creatine and creatinine metabolism.

  2000influential reference
• Regional Age Dependence of Human Brain Metabolites from Infancy to Adulthood as Detected by Quantitative Localized Proton MRS

  1999influential reference
• Metabolism of Glycine in Primary Astroglial Cells: Synthesis of Creatine, Serine, and Glutathione

  1998influential reference
• Inborn Metabolic Diseases: Diagnosis and Treatment

  1995cited by this paper
• Estimation of metabolite concentrations from localized in vivo proton NMR spectra

  1993cited by this paper

• Advancing clinical insight into creatine transporter deficiency: long term outcome and new observations from the Italian cohort.

  2026cites this paper
• Biomarkers of Creatine Metabolism in Humans: From Plasma to Saliva and Beyond

  2024cites this paper
• Rescue of myocytes and locomotion through AAV2/9-2YF intracisternal gene therapy in a rat model of creatine transporter deficiency

  2024cites this paper
• “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function

  2023cites this paper
• Characterization of seizures and EEG findings in creatine transporter deficiency due to SLC6A8 mutation

  2023cites this paper
• Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review

  2023cites this paper
• X-linked creatine transporter (SLC6A8) deficiency in females: Difficult to recognize, but a potentially treatable disease.

  2023cites this paper
• A novel variation of gamt in cerebral creatine deficiency syndrome, first complete homozygous deletion of GAMT

  2023cites this paper
• Creatine Deficiency Disorders: Phenotypes, Genotypes, Diagnosis, and Treatment Outcomes

  2023cites this paper
• Disorders of Creatine Metabolism

  2022cites this paper
• Case Report: X-Linked Creatine Transporter Deficiency in Two Saudi Brothers with Autism

  2022cites this paper
• Creatine Levels in Patients with Phenylketonuria and Mild Hyperphenylalaninemia: A Pilot Study

  2021cites this paper
• Treatment efficacy of high‐dose creatine supplementation in a child with creatine transporter (SLC6A8) deficiency

  2021cites this paper
• Creatine Supplementation in Children and Adolescents

  2021cites this paper
• Creatine supplementation and muscles: From metabolism to medical practice

  2021cites this paper
• Current and potential new treatment strategies for creatine deficiency syndromes.

  2021cites this paper
• A Treatable Cause of Intellectual Disability and Autism in a Young Child

  2020cites this paper
• Movement Disorders and Inherited Metabolic Disorders

  2020cites this paper
• Creatine transporter deficiency, an underdiagnosed cause of male intellectual disability

  2020cites this paper
• New insights into creatine transporter deficiency

  2020cites this paper
• Rescue by 4-phenylbutyrate of several misfolded creatine transporter-1 variants linked to the creatine transporter deficiency syndrome.

  2019cites this paper
• Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness

  2019cites this paper
• A Nervous System-Specific Model of Creatine Transporter Deficiency Recapitulates the Cognitive Endophenotype of the Disease: a Longitudinal Study

  2019cites this paper
• Treatment outcome of creatine transporter deficiency: international retrospective cohort study

  2018cites this paper
• Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB

  2018cites this paper
• Cognitive deficits and increases in creatine precursors in a brain‐specific knockout of the creatine transporter gene Slc6a8

  2018cites this paper
• Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

  2017cites this paper
• Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8

  2017cites this paper
• STAR syndrome plus: The first description of a female patient with the lethal form

  2017cites this paper
• Estudios de biomarcadores y de posibles terapias en la deficiencia del transportador de creatina y en la enfermedad de niemann-pick tipo c

  2016cites this paper
• Creatine transporter deficiency leads to increased whole body and cellular metabolism

  2016cites this paper
• Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency.

  2015cites this paper
• Creatine biosynthesis and transport in health and disease.

  2015cites this paper
• Creatine as a booster for human brain function. How might it work?

  2015cites this paper
• Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene.

  2015cites this paper
• Creatine Deficiency Syndromes

  2015cites this paper
• Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases.

  2014cites this paper
• Cerebral Creatine Deficiencies: A Group of Treatable Intellectual Developmental Disorders

  2014cites this paper
• A review of X-linked creatine transporter deficiency : clinical aspects and pathophysiology 4 . 2

  2014cites this paper
• clinical Proton M r s pectroscopy in central nervous s ystem Disorders 1

  2014cites this paper
• Clinical proton MR spectroscopy in central nervous system disorders.

  2014cites this paper
• Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L-arginine supplementation alternative to lysine-restricted diet.

  2014cites this paper
• X-linked creatine transporter deficiency: clinical aspects and pathophysiology

  2014cites this paper
• A novel mouse model of creatine transporter deficiency

  2014cites this paper
• Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits

  2014cites this paper
• Membrane transporters and the diseases corresponding to functional defects

  2013cites this paper
• Phenotype and genotype in 101 males with X-linked creatine transporter deficiency

  2013cites this paper
• Synthesis and biological evaluation of new creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency.

  2013cites this paper
• Inborn errors of creatine metabolism and epilepsy

  2013cites this paper
• New insights into creatine transporter deficiency: the importance of recycling creatine in the brain

  2013cites this paper
• A Novel SLC6A8 Mutation in a Large Family with X-Linked Intellectual Disability: Clinical and Proton Magnetic Resonance Spectroscopy Data of Both Hemizygous Males and Heterozygous Females.

  2013cites this paper
• A Guide to the Metabolic Pathways and Function of Metabolites Observed in Human Brain 1H Magnetic Resonance Spectra

  2013cites this paper
• Optimisation pharmacologique des dérivés de la créatine pour le traitement du déficit en transporteur de la créatine

  2013cites this paper
• Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers

  2012cites this paper
• Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency

  2012influential citation
• Creatine metabolism in urea cycle defects

  2012cites this paper
• Detection of variants in SLC6A8 and functional analysis of unclassified missense variants.

  2012cites this paper
• Long-term neuropsychologic outcome in children diagnosed with a low-grade astrocytoma

  2012cites this paper
• Phenotypic variability in a portuguese family with x-linked creatine transport deficiency.

  2012cites this paper
• SUMMARY AND DISCUSSION

  1976cites this paper