Neurogenetics: from hypokalemic periodic paralysis as an arginine deficiency to the influence of mitochondrial DNA haplogroups on therapeutic response in migraine

Abstract

Over the last 20 years neurogenetics has become more and more important and clinically relevant with regard to a definite diagnosis of certain syndromes, an understanding of the underlying pathophysiology and the development of new therapeutic principles. Hot spots in this field are channelopathies. More and more neurological disorders, ranging from familial hemiplegic migraine and episodic ataxias to muscle disorders, have been identified as channelopathies. The first article in this month’s Journal Club deals with hypokalemic periodic paralysis and the underlying voltage sensory charge loss that evidently causes the symptoms. One may therefore also call hypokalemic periodic paralysis an arginine deficiency syndrome or an argininopathy. The background will be explained below. In the second article—published in The New England Journal of Medicine—a new syndrome is described: the EAST syndrome characterised by epilepsy, ataxia, sensorineural deafness and tubulopathy, which is caused by a potassium channel mutation. This mutation has consequences for the functioning of several organs. As pointed out in the accompanying Editorial, this finding bridges the gap between medical disciplines whose general separation has been a strange tradition for decades. In the third article, the influence of mitochondrial DNA haplogroups on the therapeutic response to riboflavin in migraineurs is evaluated. This is a very interesting approach by which the response of certain groups of patients to certain drugs might be predicted in the future, allowing a more specific treatment. Finally, the author of the Journal Club recommends a so-called an occasional paper published recently in Brain on an acquired personality disorder in US presidents and UK prime ministers: hubris syndrome. Frankly speaking, this syndrome might have more devastating consequences for our well-being than many neurological disorders.