title: Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability.
abstract: Creatine deficiency syndrome due to mutations in X-linked SLC6A8 gene results in nonspecific intellectual disability (ID). Diagnosis cannot be established on clinical grounds and is often based on the assessment of brain creatine levels by magnetic resonance spectroscopy (MRS). Considering high costs of MRS and necessity of sedation, this technique cannot be used as a first level-screening test. Likewise, gene test analysis is time consuming and not easily accessible to all laboratories. In this article feasibility of urine analysis (creatine/creatinine (Cr/Crn) ratio) performed by nuclear magnetic resonance (NMR) as a first level-screening test is explored. Before running a systematic selection of cases a preliminary study for further molecular analysis is shown. NMR urine spectra (n = 1,347) of male patients with an ID without a clinically recognizable syndrome were measured. On the basis of abnormal Cr/Crn ratio, three patients with the highest values were selected for molecular analysis. A confirmatory second urine test was positive in two patients and diagnosis was further confirmed by a decreased brain creatine level and by SLC6A8 gene analysis. A de novo mutation was identified in one. Another patient inherited a novel mutation from the mother who also has a mild ID. A repeat urine test was negative in the third patient and accordingly creatine level in the brain and SLC6A8 gene analysis both gave a normal result. We conclude that Cr/Crn ratio measured by NMR for male patients represents a rapid and useful first level screening test preceding molecular analysis.
authors: Medical Genetics, Department of Biotechnology, University of Siena, Italy.
authors: Maria Antonietta
authors: MA
authors: Mencarelli
authors: Maria
authors: M
authors: Tassini
authors: Marzia
authors: M
authors: Pollazzon
authors: Antonio
authors: A
authors: Vivi
authors: Marco
authors: M
authors: Calderisi
authors: Michele
authors: M
authors: Falco
authors: Marco
authors: M
authors: Fichera
authors: Lucia
authors: L
authors: Monti
authors: Sabrina
authors: S
authors: Buoni
authors: Francesca
authors: F
authors: Mari
authors: Udo
authors: U
authors: Engelke
authors: Ron A
authors: RA
authors: Wevers
authors: Joussef
authors: J
authors: Hayek
authors: Alessandra
authors: A
authors: Renieri
mesh_terms: D001921:Brain / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis* / Q000652:urine; D003401:Creatine / Q000172:deficiency / Q000378:metabolism / Q000652:urine*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis* / Q000652:urine; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency / Q000235:genetics* / Q000652:urine; D016133:Polymerase Chain Reaction
chemical_list: D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; D003401:Creatine