Recurrent and fatal akinetic crisis in genetic-mitochondrial parkinsonisms.
OBJECTIVE
Akinetic crisis (AC) is the most severe and possibly lethal complication of parkinsonism. It occurs with an incidence of 3‰ Parkinson's disease patients per year, but it is not known whether genetically determined parkinsonism is more or less susceptible to this complication.


METHODS
In a cohort of 756 parkinsonian patients the incidence and outcome of AC was prospectively assessed. A total of 142 of the parkinsonian patients were tested for genetic mutations because of familial parkinsonism, and 20 patients resulted positive: in four the mutation definitely involved mitochondrial functions (POLG1, PINK1), two presented with LRRK2 mutation, nine presented with GBA mutation and five presented with Park 4 different mutations.


RESULTS
Akinetic crisis occurred in 30 patients for an incidence of 2.8‰ persons/year and was lethal in seven (23%), not dissimilarly from known incidences of this complication. Yet six of 30 patients were carriers of genetic mutations, one GBA, one LRRK2, one POLG1 and three PINK1. In POLG1 and PINK1 carriers, the syndrome was recurrent and was fatal in three. Incidence of AC was 3.0‰ in familiar parkinsonism, 21.2‰ in genetic parkinsonisms.


CONCLUSIONS
Our preliminary findings suggest that the incidence of AC is remarkably increased in carriers of these genetic mutations.
Neurology Clinic, Ospedale Clinicizzato, Chieti, Italy; Department of Neuroscience and Imaging, Aging Research Center, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.
L
L
Bonanni
M
M
Onofrj
E M
EM
Valente
L
L
Manzoli
M V
MV
De Angelis
M
M
Capasso
A
A
Thomas
D000368:Aged; D015331:Cohort Studies; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology*; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D005962:Glucosylceramidase; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000099202:PTEN-Induced Putative Kinase; C495280:LRRK2 protein, human; C413027:POLG protein, human
akinetic crisis; genetic parkinsonism; malignant syndrome; mitochondria