http://hdl.handle.net/10400.18/47 Fri, 17 May 2013 20:15:00 GMT 2013-05-17T20:15:00Z http://hdl.handle.net/10400.18/1557 Title: Doenças genéticas da hipertensão Authors: Jordan, Peter Thu, 11 Apr 2013 00:00:00 GMT http://hdl.handle.net/10400.18/1557 2013-04-11T00:00:00Z http://hdl.handle.net/10400.18/1366 Title: Creatine deficiency syndromes: biochemical and molecular aspects Authors: Valongo, Carla; Almeida, Lígia; Ramos, Altina; Salomons, Gajja; Jacobs, Cornelis; Vilarinho, Laura Abstract: Introduction: Creatine deficiency syndromes (CDS) represent a group of inborn errors of creatine biosynthesis: L-arginine-glycine amidinotransferase - AGAT and guanidinoacetate methyltransferase - GAMT deficiencies and transport (creatine transporter - SLC6A8 deficiency). Patients with CDS may present with mental retardation (MR), expressive speech and language delay, and epilepsy. Patients with GAMT deficiency or SLC6A8 deficiency may also exhibit autistic-like behavior. The common denominator of these disorders is the depletion of the brain creatine pool, as demonstrated by in vivo 1H-MRS. Patients and Methods: The authors studied 6,600 urine samples from Portuguese autistic children and young adults for defects in creatine metabolism. We started with the determination of guanidinoacetate and creatine in urine by GC-MS-SIM. Based on these findings, enzyme assays or DNA mutation analysis may be performed. Molecular genetic analysis for GAMT deficiency and creatine transporter deficiency is also available in our laboratory. Results: A marked excretion of guanidinoacetate in urine compatible with GAMT deficiency was observed in seven cases. Furthermore, other 15 patients showed high urinary levels of creatine/creatinine ratio what suggests a defect of SLC6A8. All GAMT deficient patients show the same mutation (c.59G>C) which suggests a founder effect in our population. Molecular genetic analysis of the SLC6A8 deficiency patients revealed a large spectrum of mutations. Discussion: So far, 22 patients with CDS were identified in our laboratory (1:300). We believe these defects are still under diagnosed, so the possibility should be considered in all children affected by unexplained MR, seizures, and speech delay. SLC6A8 defect should also be considered in males with MR and negative fragile-X testing. GAMT deficiency is treatable with oral creatine monohydrate and ornithine supplementation with arginine dietary restriction. Thu, 01 Nov 2012 00:00:00 GMT http://hdl.handle.net/10400.18/1366 2012-11-01T00:00:00Z http://hdl.handle.net/10400.18/1363 Title: Importância do Diagnóstico Pré-natal Authors: Correia, Hildeberto Thu, 24 May 2012 00:00:00 GMT http://hdl.handle.net/10400.18/1363 2012-05-24T00:00:00Z http://hdl.handle.net/10400.18/1312 Title: Optimizing the discovery of predictors of vaso-occlusion in sickle-cell disease by proteomics Authors: Lavinha, João; Charro, Nuno; Vaz, Fátima; Morais, Anabela; Penque, Deborah Abstract: Painful crises are the major sickle-cell disease (SCD) clinical manifestation probably due to significant increase in dense red blood cells (RBC) and reduction of their ability to pass through capillaries. Using proteomic strategies (see figure below), we aimed to discover novel SCD prognosis biomarkers as early predictors of the transition from steady-state to vaso-occlusive crises thus, allowing a prompt and specific therapeutic intervention. Mon, 01 Oct 2012 00:00:00 GMT http://hdl.handle.net/10400.18/1312 2012-10-01T00:00:00Z