Literatura académica sobre el tema "Neuroacanthocytosi"

IntroductionNeuroacanthocytosis is an infrequent cause of both neurological and psychiatric manifestations, and acanthocytes, which are a special form of spiculated red blood cells. Clinically significant psychopathology, ranging from behavioural disturbance to frank psychiatric illness, has been reported to occur in up to 60% of ChAc patients.MethodsA review was conducted aiming to clarify the physiopathology of this illness and its clinical features in order to distinguish neuroacanthocytosis from other neurological or psychiatric diseases. The literature search was conducted in PubMed data reviewing articles dating between 2010 and 2016.Results– Neuroacanthocytosis autosomal recessive disorder associated with mutations or deletions in the VPS13A gene on chromosome 9q, which codes for the membrane protein chorein. Chorein is strongly expressed in the brain. Chorein loss particularly affects the basal ganglia, especially the caudate nucleus and putamen;– Dysexecutive syndromes, OCD, depression and possibly psychosis, which may precede the frank motor and cognitive impairment;– The most recently developed treatment for neuroacanthocytoses is the use of deep-brain stimulation (DBS), with stimulation of the globus pallidus internus.ConclusionsWhile conducting a neurological exam, secondary causes of psychosis have to be included in the differential diagnosis. It is important to notice the possible confusion between tardive dyskinesia and a primary movement disorder. It should be necessary to investigate all de novo movement disorders in psychotic patients in order to eliminate etiologies other than iatrogenic ones.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Huntington's disease and neuroacanthocytosis may present similar clinical and MRI features. It is important to differentiate these findings since treatment and prognosis vary vastly between them. The aim of this article is to familiarize radiologists with the differentiating features of Huntington's disease and various diseases comprising neuroacanthocytosis. A 40-year-old Indian man with extrapyramidal symptoms was referred for MRI. The clinical diagnosis was Huntington's disease, but there were a few atypical clinical features such as a history of biting the tongue, tics, marked hyporeflexia and lower limb muscle wasting. MR showed atrophy of the caudate nucleus and putamen with iron deposition in the basal ganglia, which can be seen in Huntington's disease and in neuroacanthocytosis. An increased blood acanthocyte level was subsequently confirmed. Further work-up revealed increased serum creatine phosphokinase levels, normal serum lipoprotein levels and depressed K cell antigen activity on serological studies, confirming the diagnosis of McLeod syndrome. McLeod syndrome is one of the distinct phenotypes of neuroacanthocytosis. Neuroacanthocytosis is a group of disorders with increased serum acanthocyte counts and neurological involvement. Various causes of neuroacanthocytosis are discussed. It is important to consider the possibility of neuroacanthocytosis when features typical of Huntington's disease are encountered on imaging.

ABSTRACT:Two patients with neuroacanthocytosis are described. One presented with parkinsonism and the other resembled diurnal dystonia of the Segawa type. Both patients responded well to dopaminomimetic therapy. A PET scan with fluorodopa revealed a nigrostriatal deficit in the first patient.

Il termine neuroacantocitosi (NA) raggruppa diverse malattie genetiche rare che condividono manifestazioni neurologiche simili e la presenza di globuli rossi stellati nella circolazione periferica, gli acantociti. Le due principali malattie classificate come NA sono Corea acantocitosi (ChAc) e sindrome di McLeod (MLS). Poiché la presenza di acantociti è una caratteristica comune di questi disordini, lo studio dei meccanismi alla base della loro formazione può aiutare a comprendere la patogenesi delle NA. In questa tesi viene presentata una serie di studi sui meccanismi di signaling e sulle modificazioni strutturali di globuli rossi di pazienti di ChAc e MLS. Nel primo studio abbiamo analizzato con tecniche di proteomica la fosforilazione in tirosina di globuli rossi di pazienti affetti da ChAc . Nei globuli rossi di questi pazienti abbiamo riscontrato un aumento della fosforilazione in tirosina su diverse proteine di membrana e legate alla membrana tra cui banda 3, β-spectrina e adducina. In particolare, la fosforilazione sul residuo Tyr-904 della banda 3, target della chinasi Lyn, era molto elevata, mentre sul residuo Tyr-8 della stessa proteina, target della chinasi Syk, non abbiamo riscontrato un aumento della fosforilazione. Nei pazienti di ChAc, la fosforilazione della banda 3 da parte di Lyn è indipendente dal meccanismo canonico di fosforilazione sequenziale mediato da Syk. Le alterazioni dell’organizzazione delle proteine di membrana correlate con ChAc sembrano quindi essere il risultato di un aumento della fosforilazione in tirosina che porta a cambiamenti nel legame della banda 3 con i ponti multiproteici tra la membrana e il citoscheletro. Proponiamo quindi quest’alterazione nell’associazione tra membrana e citoscheletro mediata da fosforilazione in tirosina come un nuovo meccanismo che porta alla formazione di acantociti in ChAc. Nel secondo studio abbiamo combinato i nostri set di dati fosfo-proteomici su eritrociti di pazienti di ChAc e MLS con l’analisi topologica di network proteici per predirre quali sub-network della trasduzione del segnale possano essere coinvolti nella formazione degli acantociti. Abbiamo identificato tutte le interazioni che legano le due proteine mutate nelle due patologie in esame (rispettivamente coreina e XK) con le proteine differenzialmente fosforilate dei nostri dati sperimentali. Quindi, abbiamo analizzato nello specifico solo cluster di proteine coinvolte nella trasduzione del segnale che interagiscono molto strettamente tra loro e che possono essere coinvolte nella formazione di acantociti in entrambe le patologie. Abbiamo identificato un cluster di 14 chinasi che possono essere coinvolte in tale processo e meritano ulteriori approfondimenti. Come studio preliminare nel contesto di una collaborazione internazionale abbiamo analizzato globuli rossi da pazienti affetti da Neurodegenerazione con Accumulo di Ferro nel Cervello (NBIA) e di loro parenti di primo grado. Il nostro scopo era quello di determinare se fossero presenti acantociti nei pazienti e nei soggetti correlati ma privi di sintomi clinici e di studiare le caratteristi che strutturali dei loro eritrociti. Nell’ultimo studio abbiamo validato con l’applicazione a tecniche di analisi proteomica un nuovo copolimero basato su acrilamide e polivinil alcool modificato con gruppi olefinici. Questo nuovo idrogel è semplice da maneggiare anche a basse concentrazioni e la sua macroporosità lo rende particolarmente adatto alla separazione di proteine ad alto peso molecolare quale la coreina.
Neuroacanthocytosis (NA) is a group of rare genetic disorders that share similar neurological clinical manifestations and the presence of thorny red cells in the peripheral circulation, the acanthocytes. The two core NA diseases are Chorea-Acanthocytosis (ChAc) and McLeod Syndrome (MLS). Since acanthocytes are an hallmark of NA, studying the mechanisms underlying the generation of acanthocytes might shed light on the pathogenesis of NA syndromes. Here, we present a set of studies on the signaling mechanisms and structural changes in red cells from ChAc and MLS patients. In the first study, we evaluated tyrosine phosphorylation of red cells from ChAc patients by proteomics analysis. Increased Tyr-phosphorylation state of several membrane proteins including band 3, β-spectrin and adducin was found in ChAc RBCs. In particular, band 3 was highly phosphorylated on the Tyr-904 residue, a functional target of Lyn, but not on Tyr-8, a functional target of Syk. In ChAc RBCs band 3 Tyr-phosphorylation by Lyn was independent of the canonical Syk mediated pathway. The ChAc-associated alterations in RBC membrane-protein organization appear to be the result of increased Tyr-phosphorylation leading to altered linkage of band 3 to the junctional complexes involved in anchoring the membrane to the cytoskeleton. We propose this altered association between cytoskeleton and membrane proteins as a novel mechanism in the generation of acanthocytes in ChAc. In the second study, we combined phosphoproteomics datasets on ChAc and MLS with network topology analysis to predict signaling sub-networks involved in acanthocyte generation. We identified all the interactomic shortest paths linking the two proteins mutated in NA syndromes, respectively chorein and XK, to the differentially phosphorylated proteins in our proteomics data. Then, we refined the analysis considering only restricted clusters of highly interacting signaling proteins which can be involved in acanthocyte formation in both diseases. We identified a cluster of 14 kinases that might be related to red cell shape alterations and deserve further investigation. As preliminary study in the context of an international collaboration we analyzed red cells from Neurodegeneration with Brain Iron Accumulation (NBIA) patients and their first degree relatives. Our aim was to assess the presence of acanthocytes in these subjects and to study their structural characteristics. In the last study, we validated a new co-polymer based on acrylamide and polyvinyl alcohol bearing olefinic moieties in proteomic analysis of red cells. This new hydrogel is easy to handle and its macroporosity makes it suitable for the separation of high molecular weight proteins such as chorein.