title: X-linked creatine transporter defect: an overview.
abstract: In 2001 we identified a new inborn error of metabolism caused by a defect in the X-linked creatine transporter SLC6A8 gene mapped at Xq28 (SLC6A8 deficiency, McKusick 300352). An X-linked creatine transporter defect was presumed because of (1) the absence of creatine in the brain as indicated by proton magnetic resonance spectroscopy (MRS); (2) the elevated creatine levels in urine and normal guanidinoacetate levels in plasma, ruling out a creatine biosynthesis defect; (3) the absence of an improvement on creatine supplementation; and (4) the fact that the pedigree suggested an X-linked disease. Our hypothesis was proved by the presence of a hemizygous nonsense mutation in the male index patient and by the impaired creatine uptake by cultured fibroblasts. Currently, at least 7 unrelated families (13 male patients and 13 carriers) with a SLC6A8 deficiency have been identified. Four families come from one metropolitan area. This suggests that SLC6A8 deficiency may have a relatively high incidence. The hallmarks of the disorder are X-linked mental retardation, expressive speech and language delay, epilepsy, developmental delay and autistic behaviour. In approximately 50% of the female carriers, learning disabilities of varying degrees have been noted.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. g.salomons@vumc.nl
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
authors.forename: S J M
authors.initials: SJ
authors.lastname: van Dooren
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: D
authors.initials: D
authors.lastname: Marsden
authors.forename: C
authors.initials: C
authors.lastname: Schwartz
authors.forename: K M
authors.initials: KM
authors.lastname: Cecil
authors.forename: T J
authors.initials: TJ
authors.lastname: DeGrauw
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D001692:Biological Transport; D041321:Chromosomes, Human, X; D003401:Creatine / Q000172:deficiency / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050480:Plasma Membrane Neurotransmitter Transport Proteins
chemical_list: D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; C080679:creatine transporter; D003401:Creatine