Chorea-acanthocytosis is closely related to diseases with Parkinsonism, dementia, and ataxia

Prominent research published during 2018 in Annals of Neurology has marked a major milestone in NA disease research, confirming that the VPS13 family of genes is implicated not just in NA group diseases like ChAc, but also in dementia and Parkinson's.


Shortly after the gene mutated in chorea-acanthocytosis (ChAc) was discovered in 2001, Antonio Velayos-Baeza from the Monaco group in Oxford started to look for DNA sections homologous to the CHAC gene, as it was called initially. In 2004 he reported about such related genes and named the whole group the VPS13 family, starting with the ChAc gene VPS13A, followed by VPS13B through D. He recognized that VPS13B was identical with COH1, a gene described the year before as responsible for Cohen syndrome. This is a condition quite unlike ChAc, namely a neurodevelopmental disorder that manifests at birth, e.g. with peculiar facial features and eye problems, and that lacks the neurodegenerative features of ChAc which start progressing from early adulthood.


For a long time, the ultra-rare disease ChAc thus appeared to be a lone, disconnected condition – but this situation has now come to an end. First, various hints appeared between 2012 and 2016 that VPS13C might be involved in dementia and in Parkinson's disease. Yet with two papers on VPS13D from 2018, prominently published in Annals of Neurology, it has finally become clear that ChAc has found its family of related neurodegenerative conditions.


A family reunion of sorts was sponsored by the German Society of Neurology and took the form of a 90 minute session at the Messe Berlin on November 1, 2018. This first meeting entirely devoted to the recent progress in VPS13 research at a major scientific convention heard members from the leading labs in the field discuss their current insights. Margit Burmeister apparently had the longest distance to travel to address the session chaired by Adrian Danek (Munich, Germany) and Andreas Hermann (Rostock, Germany). Fortunately, however, Dr. Burmeister was on sabbatical in Germany and came from Heidelberg instead of from her institute in Ann Arbor, Michigan, USA. She spoke about the ataxic movement disorders resulting from VPS13D mutations. Stefanie Smolders joined from the lab of Christine Van Broeckhoven in Antwerp, Belgium, and reported about the autosomal recessive VPS13C mutations in their cases of Lewy body disease, a subtype of Parkinson's. Volker Haucke from Berlin covered the faulty cell biology that underlies Cohen syndrome and Andreas Hermann summarized the current knowledge about ChAc.


The overall picture that emerged suggests that the VPS13 family is essential for the transfer of membrane elements (probably mainly lipids) among several of the various organelles in the myriads of cells that make up the human body.


Much further work will be necessary to fully unravel the details of these mechanisms and to translate them into medical treatment. In any case, the Berlin meeting has reunited ChAc with its family and was another building block to achieve the critical mass of international scientific effort that will eventually lead to cures for VPS13 diseases.



Margot Burmeister, Stefanie Smolders, Volker Haucke, Adrian Danek and Andreas Hermann
Margot Burmeister, Stefanie Smolders, Volker Haucke, Adrian Danek and Andreas Hermann
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