Journal Article

Plasma metabolomics reveals a diagnostic metabolic fingerprint for mitochondrial aconitase (ACO2) deficiency

Abela, Lucia, Papuc, Sorina Mihaela, Spiegel, Ronen, Steindl, Katharina, Crowther, Lisa M., Simmons, Thomas Luke, Joset, Pascal, Zehavi, Yoav, Plecko, Barbara, Klein, Andrea, Rauch, Anita

2017

Overview

Mitochondrial respiratory chain dysfunction has been identified in a number of neurodegenerative disorders. Infantile cerebellar-retinal degeneration associated with mutations in the mitochondrial aconitase 2 gene (ACO2) has been recently described as a neurodegenerative disease of autosomal recessive inheritance. To date there is no biomarker for ACO2 deficiency and diagnosis relies on genetic analysis. Here we report global metabolic profiling in eight patients with ACO2 deficiency. Using an LC-MS-based metabolomics platform we have identified several metabolites with affected plasma concentrations including the tricarboxylic acid cycle metabolites cis-aconitate, isocitrate and alpha-ketoglutarate, as well as phosphoenolpyruvate and hydroxybutyrate. Taken together we report a diagnostic metabolic fingerprint for mitochondrial aconitase 2 deficiency.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 4-Hydroxynonenal / Abnormalities / Acetic acid / Acidosis / Aconitase / Aconitate Hydratase - deficiency / Aconitate Hydratase - genetics / Aconitic Acid - blood / Adenine / Adenosine triphosphate / Adolescent / Aging / Aging (artificial) / Alanine / Alzheimer's disease / AMP / AMP-activated protein kinase / Analysis / Antioxidants / Assaying / Ataxia / ATP / Autosomal recessive inheritance / Biocompatibility / Bioindicators / Biology and Life Sciences / Biomarkers / Biomarkers - blood / Biosynthesis / Blood plasma / Brain / Brain research / Carbohydrates / Carbon dioxide / Catalysis / Cerebellum / Child / Child, Preschool / Children / Children & youth / Computer programs / Control / Dehydrogenase / Dehydrogenases / Deoxyribonucleic acid / Diagnosis / DNA / Enzymatic activity / Enzymes / Families & family life / Fatty acids / Female / Gene expression / Genetic screening / Genetics / Guardians / Health aspects / Heredodegenerative Disorders, Nervous System - blood / Heredodegenerative Disorders, Nervous System - diagnosis / Hospitals / Humans / Huntingtons disease / Hydroxybutyrates - blood / Inactivation / Infections / Insects / Iron / Isocitrates - blood / Ketoglutaric acid / Ketoglutaric Acids - blood / Kidneys / Kinases / Liver / Lobes / Male / Medical diagnosis / Medicine / Metabolism / Metabolites / Metabolomics / Metabolomics - methods / Missense mutation / Mitochondria / Mitochondrial DNA / Movement disorders / Mutation / Neurodegeneration / Neurodegenerative diseases / Neurology / Oxidative stress / Paralysis / Pediatrics / People and Places / Pharmacology / Phosphoenolpyruvate - blood / Plasmas (physics) / Poisoning / Proteins / Proteomics / Respiration / Retina / Urine