Changes in Red Blood Cell membrane lipid composition: A new perspective into the pathogenesis of PKAN

Manar Aoun, Paola Antonia Corsetto, Guillaume Nugue, Gigliola Montorfano, Emilio Ciusani, David Crouzier, Penelope Hogarth, Allison Gregory, Susan Hayflick, Giovanna Zorzi, Angela Maria Rizzo, Valeria Tiranti

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). The PANK2 catalyzes the first step of coenzyme A (CoA) biosynthesis, a pathway producing an essential cofactor that plays a key role in energy and lipid metabolism. The majority of PANK2 mutations reduces or abolishes the activity of the enzyme. In around 10% of cases with PKAN, the presence of deformed red blood cells with thorny protrusions in the circulation has been detected. Changes in membrane protein expression and assembly during erythropoiesis were previously explored in patients with PKAN. However, data on red blood cell membrane phospholipid organization are still missing in this disease. In this study, we performed lipidomic analysis on red blood cells from Italian patients affected by PKAN with a particular interest in membrane physico-chemical properties. We showed an increased number of small red blood cells together with membrane phospholipid alteration, particularly a significant increase in sphingomyelin (SM)/phosphatidylcholine (PC) and SM/phosphatidylethanolamine (PE) ratios, in subjects with PKAN. The membrane structural abnormalities were associated with membrane fluidity perturbation. These morphological and functional characteristics of red blood cells in patients with PKAN offer new possible tools in order to shed light on the pathogenesis of the disease and to possibly identify further biomarkers for clinical studies.

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Jun 2017


  • Biomarkers
  • Erythrocytes
  • Membrane
  • Mitochondria
  • NBIA
  • Neurodegenerative diseases
  • Oxidized lipids
  • PKAN
  • Phospholipids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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