Centaur 1948

Digitised by the Faculty of the Veterinary Scienc

Metabolomics-Based Screening of Inborn Errors of Metabolism: Enhancing Clinical Application with a Robust Computational Pipeline

Contains fulltext : 238438.pdf (Publisher’s version ) (Open Access

C677T mutation of methylenetetrahydrofolate reductase gene determined in blood or plasma by multiple-injection capillary electrophoresis and laser-induced fluorescence detection

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Genetics of hyperhomocysteinaemia in cardiovascular disease.

Item does not contain fulltextHomocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme deficiencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B(12) and vitamin B(6), may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also influenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date

Accurate and rapid "multiplex heteroduplexing" method for genotyping key enzymes involved in folate/homocysteine metabolism.

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Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

Item does not contain fulltextAlthough the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 mumol/l (normal: 20-55 muM) and total carnitine level had dropped to 12.7 mumol/l (normal: 25-65 muM). Transient carnitine deficiency was not likely anymore and DNA mutation analysis of the OCTN2 (SLC22A5) gene showed a homozygous c.136C>T (p.P46S) mutation, confirming the diagnosis of primary carnitine deficiency. We would like to emphasize that neonates with a primary carnitine deficiency might present with relatively high levels of total carnitine due to placental carnitine transfer, and also draw the attention to the importance of regular follow-up and the significance of genetic diagnostics in patients with a nonclassical presentation