The urinary organic acids profile in single large-scale mitochondrial DNA deletion disorders

Michela Semeraro, Sara Boenzi, Rosalba Carrozzo, Daria Diodato, Diego Martinelli, Giorgia Olivieri, Giacomo Antonetti, Elisa Sacchetti, Giulio Catesini, Cristiano Rizzo, Carlo Dionisi-Vici

Research output: Contribution to journalArticlepeer-review


Single large-scale mitochondrial DNA deletions disorders are classified into three main phenotypes with frequent clinical overlap: Pearson marrow-pancreas syndrome (PMS), Kearns-Sayre syndrome (KSS) and chronic progressive external ophtalmoplegia (PEO). So far, only few anecdotal studies have reported on the urinary organic acids profile in this disease class. In this single-center retrospective study, we performed quantitative evaluation of urinary organic acids in a series of 15 pediatric patients, 7 with PMS and 8 with KSS. PMS patients showed an organic acids profile almost constantly altered, whereas KSS patients frequently presented with normal profiles. Lactate, 3-hydroxybutyrate, 3-hydroxyisobutyrate, fumarate, pyruvate, 2-hydroxybutyrate, 2-ethyl-3-hydroxypropionate, and 3-methylglutaconate represented the most frequent metabolites observed in PMS urine. We also found novel metabolites, 3-methylglutarate, tiglylglycine and 2-methyl-2,3-dihydroxybutyrate, so far never reported in this disease. Interestingly, patients with a disease onset as PMS evolving overtime into KSS phenotype, presented persistent and more pronounced alterations of organic acid signature than in patients with a pure KSS phenotype. Our study shows that the quantitative analysis of urinary organic acid profile represents a helpful tool for the diagnosis of PMS and for the differential diagnosis with other inherited diseases causing abnormal organic acidurias.

Original languageEnglish
Pages (from-to)156-160
Number of pages5
JournalClinica Chimica Acta
Publication statusPublished - Jun 2018


  • 3-Hydroxybutyric Acid/urine
  • Acyl-CoA Dehydrogenase, Long-Chain/deficiency
  • Adolescent
  • Child
  • Child, Preschool
  • DNA, Mitochondrial/genetics
  • Fumarates/urine
  • Glutarates/urine
  • Humans
  • Hydroxybutyrates/urine
  • Infant
  • Kearns-Sayre Syndrome/diagnosis
  • Lactic Acid/urine
  • Lipid Metabolism, Inborn Errors/diagnosis
  • Mitochondrial Diseases/diagnosis
  • Muscular Diseases/diagnosis
  • Pyruvic Acid/urine
  • Retrospective Studies
  • Valerates/urine


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