Recurrent and fatal akinetic crisis in genetic-mitochondrial parkinsonisms

• Published in: European journal of neurology Vol. 21; no. 9; pp. 1242 - 1246
• Main Authors: Bonanni, L., Onofrj, M., Valente, E. M., Manzoli, L., De Angelis, M. V., Capasso, M., Thomas, A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2014; John Wiley & Sons, Inc
• Subjects: Aged; akinetic crisis; Cohort Studies; DNA Polymerase gamma; DNA-Directed DNA Polymerase - genetics; Female; genetic parkinsonism; Glucosylceramidase - genetics; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Male; malignant syndrome; Medical research; Middle Aged; mitochondria; Mitochondria - genetics; Mutation; Mutation - genetics; Parkinsonian Disorders - genetics; Parkinsonian Disorders - pathology; Protein Kinases - genetics; Protein-Serine-Threonine Kinases - genetics; malignant syndrome; akinetic crisis; genetic parkinsonism; mitochondria
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/ene.12364

Background and purpose 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.