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Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes

De Franceschi, Luciaa; Bosman, Giel J.C.G.M.b; Mohandas, Narlac

Current Opinion in Hematology: May 2014 - Volume 21 - Issue 3 - p 201–209
doi: 10.1097/MOH.0000000000000035

Purpose of review This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS).

Recent findings Although molecular defects associated with neuroacanthocytosis have been identified recently, their pathophysiology and the related RBC abnormalities are largely unknown. Studies in ChAc RBCs have shown an altered association between the cytoskeleton and the integral membrane protein compartment in the absence of major changes in RBC membrane composition. In ChAc RBCs, abnormal Lyn kinase activation in a Syk-independent fashion has been reported recently, resulting in increased band 3 tyrosine phosphorylation and perturbation of the stability of the multiprotein band 3-based complexes bridging the membrane to the spectrin-based membrane skeleton. Similarly, in MLS, the absence of XK-protein, which is associated with the spectrin–actin–4.1 junctional complex, is associated with an abnormal membrane protein phosphorylation state, with destabilization of the membrane skeletal network resulting in generation of acanthocytes.

Summary A novel mechanism in generation of acanthocytes involving abnormal Lyn activation, identified in ChAc, expands the acanthocytosis phenomenon toward protein–protein interactions, controlled by phosphorylation-related abnormal signaling.

aDepartment of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy

bDepartment of Biochemistry, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

cRed Cell Physiology Laboratory, New York Blood Center, New York, New York, USA

Correspondence to Lucia De Franceschi, MD, Department of Medicine, University of Verona and AOUI, Policlinico GB Rossi, P.le L Scuro, 10; 37134 Verona, Italy. Tel: +39 0458124918; fax: +39 0458027473; e-mail:

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins