Unequivocal terms are a prerequisite for confronting the world and communicating about it. In 1952, Karl Singer, a hematologist from Vienna and Chicago, introduced the Greek word for thorn/prickle (ἄκανθα) to describe an as yet novel appearance of red cells. The associated disease “acanthocytosis” (of Bassen and Kornzweig) was quickly renamed to abetalipoproteinemia, once its biomarker signature had been discovered.

As the peculiar “thorny” erythrocyte shape was observed also with normal lipoproteins, the existence of further conditions of acanthocytosis (now turned into a mere finding and no longer a singular disease entity) became obvious. Apart from the occurrence in severe liver disease (with “spur cell” as alternative designation for the erythrocyte deformation), various neurological findings were found in association with acanthocytosis. These cases were designated to suffer from neuroacanthocytosis or Levine-Critchley syndrome. The often-quoted series of Hardie et al. (1991), however, has since been found to be genetically heterogeneous. This series contains cases due to mutations in XK, VPS13A, and PANK2. In addition, the index families of Levine et al. (1968) and of Critchley et al. (1968) are now known to harbor mutations of XK and of VPS13A, respectively. (Kaestner Tremor and Other Hyperkinetic Movements DOI: 10.5334/tohm.826 3)

“Neuroacanthocytosis” retains some usefulness [1] as a tentative label while working up a complex case, [2] as an umbrella term to group conditions that are related because their molecular substrates interact (as shown for the XK/McLeod and chorein/VPS13A proteins), and [3] as a tool for advocating for patients and their carers. “Neuroacanthocytosis”, however, does not represent a final medical diagnosis and must be shunned if precision medicine is the goal. Further, its continued use perpetuates the problem of constructing and imagining an entity based on a mere word – as not all patients with VPS13A and XK mutations present with acanthocytosis or with neurological findings, diagnostic delays result from fixation on the outdated term. The terms “XK disease”, “VPS13A disease”, and “PKAN” – even if somewhat “bloodless” – are superior if personalized medicine and, in particular, personalized treatment is pursued. The individual patient with one of these rare and ultra-rare diseases deserves a definite, genetically based diagnosis.

[Note: This article was taken from the Proceedings of the "Eleventh International Meeting on Neuroacanthocytosis Syndromes" published by Tremor and Other Hyperkinetic Movements and compiled by Lars Kaestner. You may find the full proceedings at: https://tremorjournal.org/articles/10.5334/tohm.826. Photo on the right: Lars Kaestner and Adrian Danek.]