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27-02-2014 | Parkinson's disease | Article

Genetic clue to akinetic crisis cause


Free abstract

medwireNews: The risk of akinetic crisis (AC) in patients with Parkinson’s disease (PD) may be linked to specific genetic mutations, research suggests.

AC is a rare complication of PD; it occurred in just 30 of 756 patients in the study during an average follow-up lasting more than 14 years, giving an overall incidence of 2.8 per 1000 person–years.

The incidence was no higher in the 142 patients with familial PD than in the 614 with idiopathic PD, at respective rates of 3.0 and 2.7 per 1000 person–years. But all six cases that occurred in patients with familial PD occurred in patients with known genetic contributors to PD, at a rate of 21.2 per 1000 person–years.

Four of these patients carried mutations affecting mitochondrial function (one in the POLG1 gene, three in PINK1), and all four of these patients had recurrent AC, with three dying of the last episode.

Precipitating events for AC in patients with genetic mutations included infections, surgery, bone trauma with fracture and gastroenteritis, report Astrid Thomas (University G. d’Annunzio of Chieti-Pescara, Italy) and team.

The other two patients had mutations in GBA and LRRK2. Neither patient had recurrent AC but AC was fatal in the patient with the LRRK2 mutation.

These mutations might seem to contradict the implication that mitochondrial dysfunction is a major driver of AC, say Thomas et al in the European Journal of Neurology. However, they note that one mutant form of LRRK2 reportedly causes mitochondrial defects, and mitochondrial dysfunction has also been found in association with GBA mutation.

“Therefore the main conclusion is that our findings point to mitochondrial genetically driven dysfunction as one of the most probable underlying causes of AC,” say the researchers.

They add that to confirm this hypothesis “further studies will be needed, considering wider populations, assessing all cases of AC for genetic mutations and considering the risk of underestimation of genetic mutations because of reduced penetrance or recessive inheritance.”

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Eleanor McDermid, Senior medwireNews Reporter

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