الفهرس 
Title: Biochemical characterisation and screening for creatine deficiency syndromes in children with autistic spectrum disorders or epilepsy
AbstractOnly 14 pages are availabe for public view
 |  | from | 188 |  |  |
| | | from | 188 | | |
Abstract
Background: Creatine deficiency syndromes (CDSs) are disorders affecting creatine synthesis or transport. Several methods have been developed to measure GAA and creatine in different body fluids such as gas chromatography mass spectrometry (GC-MS) and High-pressure liquid chromatography mass spectrometry (HPLC/MS). Confirming the diagnosis of CDSs is performed by sequencing of the corresponding gene or functional enzymatic assay. The main aim of the current study was to find the most reliable, accurate, and cost-effective screening method for CDSs. Additionally, this study aimed at discovering novel variant in AGAT, GAMT and SLC6A8 genes in Egyptian patients and investigating other possible genes that could contribute to the development of CDSs. Finally, this study was performed to estimate the prevalence of CDSs in a cohort of Egyptian patients presenting with the clinical signs and symptoms of possible CDSs. Subjects and methods: This study was conducted on 150 subjects with clinical signs and symptoms highly suspected of CDSs. Metabolic profiling of all urine samples was performed using three techniques: 1) GC/MS 2) Ultra high-pressure (or performance) liquid chromatography - Mass Spectrometry (UHPLC/MS) and 3) Nuclear Magnetic Resonance spectroscopy (NMR).Ten cases had positive screening test by GC/MS, UHPLC/MS and/or NMR and subsequently underwent clinical exome sequencing by next generation sequencing (NGS) technique. Results: UHPLC-MS and NMR methods had positive linear correlation with GC- MS.The linearity of creatine and GAA by the two methods covered and exceeded the values normally found in the urine.The limit of quantification for creatine and GAA respectively was 0.25 æmol/L and 0.25 æmol/L by UHPLC-MS and 10 æmol/L and 50 æmol/L by NMR