title: X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.
abstract: We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter. The male index patient presented with developmental delay and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate levels were normal. In three female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present, to various extents. Fibroblasts from the index patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake. The three female relatives were heterozygous for this mutation in SLC6A8, which has been mapped to Xq28.
authors.affiliation: VU Medical Center, Metabolic Unit, Department of Clinical Chemistry, 1081 HV Amsterdam, The Netherlands.
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
authors.forename: S J
authors.initials: SJ
authors.lastname: van Dooren
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: K M
authors.initials: KM
authors.lastname: Cecil
authors.forename: W S
authors.initials: WS
authors.lastname: Ball
authors.forename: T J
authors.initials: TJ
authors.lastname: Degrauw
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002874:Chromosome Mapping; D018389:Codon, Nonsense / Q000235:genetics*; D003401:Creatine / Q000032:analysis / Q000097:blood / Q000172:deficiency* / Q000652:urine; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D005347:Fibroblasts; D008040:Genetic Linkage / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009123:Muscle Hypotonia / Q000235:genetics; D010375:Pedigree; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C080679:creatine transporter; D003401:Creatine