title: X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism.
abstract: We describe the first two unrelated Spanish patients with creatine transporter deficiency initially identified by brain proton magnetic resonance spectroscopy (MRS). The clinical phenotype was characterized by severe mental retardation, epilepsy, autism, severe speech delay and absence of brain creatine by MRS. Urine creatine/creatinine ratio was increased and creatine uptake in fibroblasts was impaired in both patients. On DNA sequence analysis of the SLC6A8/creatine transporter gene, one hemizygous mutation was found in each patient: one mutation was novel and consisted of a deletion of two nucleotides c.878-879delTC in exon 5, resulting in a frameshift (p.Lys293fsX3), and in the other patient a known deletion of three nucleotides 1222-1224delTTC in exon 8 resulting in p.Phe408del. Creatine treatment for one year failed to improve the neurological symptoms and was associated with a striking increase in body weight in both patients (13 and 16 kg, respectively).
authors.affiliation: Department of Neuropediatrics, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Póo-Argüelles
authors.forename: A
authors.initials: A
authors.lastname: Arias
authors.forename: M A
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: A
authors.initials: A
authors.lastname: Ribes
authors.forename: R
authors.initials: R
authors.lastname: Artuch
authors.forename: A
authors.initials: A
authors.lastname: Sans-Fito
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: G
authors.initials: G
authors.lastname: Salomons
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000175:diagnosis* / Q000235:genetics; D001921:Brain / Q000473:pathology; D002648:Child; D041321:Chromosomes, Human, X; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000235:genetics; D013030:Spain
chemical_list: D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; C080679:creatine transporter