Patients with organic acidaemias have an altered thiol status

• Published in: Acta Paediatrica Vol. 101; no. 11; pp. e505 - e508
• Main Authors: Salmi, Heli, Leonard, James V., Lapatto, Risto
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2012; Wiley Subscription Services, Inc
• Subjects: Adolescent; Amino Acid Metabolism, Inborn Errors - blood; Amino Acid Metabolism, Inborn Errors - metabolism; Biomarkers - blood; Case-Control Studies; Cells, Cultured; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cysteine; Cysteine - blood; Cysteine - metabolism; Fibroblasts - metabolism; Glucosephosphate Dehydrogenase - blood; Glutathione; Glutathione - blood; Glutathione - deficiency; Glutathione - metabolism; Glutathione Peroxidase - blood; Glutathione Reductase - blood; Glutathione Transferase - blood; Humans; Inborn errors of metabolism; Infant; Isovaleryl-CoA Dehydrogenase - blood; Isovaleryl-CoA Dehydrogenase - deficiency; Oxidative Stress; Propionic Acidemia - blood
• ISSN: 0803-5253; 1651-2227
• DOI: 10.1111/j.1651-2227.2012.02799.x

Aim:  To study whether patients with organic acidaemias have altered glutathione (GSH) levels and thiol redox status. Previously, organic acidaemias have been associated with mitochondrial dysfunction and oxidative stress, suggesting an increased need for antioxidant protection. Furthermore, dietary protein restriction may impair GSH synthesis in these diseases. Methods:  In children with organic acidaemias, cysteine (CYSH) and GSH concentrations in plasma and erythrocytes as well as erythrocyte GSH peroxidase, GSH reductase, GSH S‐transferase and glucose‐6‐phosphate dehydrogenase activities were studied. In addition, GSH and CYSH concentrations were measured in human fibroblasts exposed to organic acids. Results:  Patients with organic acidaemias had lower plasma GSH concentration than their controls. A greater fraction of GSH and CYSH in the patients’ plasma was oxidized, suggesting decreased GSH synthesis and increased consumption. Conclusion:  Patients with organic acidaemias may have a relative GSH deficiency. With further research, these results could also have therapeutic implications.