Dissecting the neuronal vulnerability underpinning Alpers' syndrome: a clinical and neuropathological study.

Brain Pathology
Hannah HayhurstNichola Z Lax

Abstract

Alpers' syndrome is an early-onset neurodegenerative disorder often caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG) which is essential for mitochondrial DNA (mtDNA) replication. Alpers' syndrome is characterized by intractable epilepsy, developmental regression and liver failure which typically affects children aged 6 months-3 years. Although later onset variants are now recognized, they differ in that they are primarily an epileptic encephalopathy with ataxia. The disorder is progressive, without cure and inevitably leads to death from drug-resistant status epilepticus, often with concomitant liver failure. Since our understanding of the mechanisms contributing the neurological features in Alpers' syndrome is rudimentary, we performed a detailed and quantitative neuropathological study on 13 patients with clinically and histologically-defined Alpers' syndrome with ages ranging from 2 months to 18 years. Quantitative immunofluorescence showed severe respiratory chain deficiencies involving mitochondrial respiratory chain subunits of complex I and, to a lesser extent, complex IV in inhibitory interneurons and pyramidal neurons in the occipital cortex and in Purkinje c...Continue Reading

References

Jan 1, 1978·Annals of Neurology·M SalcmanS Gilman
Dec 1, 1992·Annals of Neurology·A R BickneseW E Dodson
Aug 28, 1989·Brain Research·N C de LanerolleD D Spencer
Jan 1, 1970·Acta Neuropathologica·K Jellinger, F Seitelberger
Aug 1, 1984·Annals of Neurology·O Lindvall, B Nilsson
Mar 1, 1995·Journal of Neurology, Neurosurgery, and Psychiatry·B N HardingA E Harding
Aug 1, 1994·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·G B YoungW T Blume
May 22, 2002·Archives of Neurology·Ricardo A TeixeiraFernando Cendes
Oct 10, 2003·Brain : a Journal of Neurology·J I ArellanoJ DeFelipe
May 4, 2004·Annals of Neurology·Robert K Naviaux, Khue V Nguyen
May 13, 2005·Human Molecular Genetics·Nicole HanceAleksandra Trifunovic
Jun 2, 2005·Trends in Neurosciences·Zsófia Maglóczky, Tamás F Freund
Apr 28, 2006·Brain : a Journal of Neurology·Charalampos TzoulisLaurence A Bindoff
Jan 16, 2008·Archives of Neurology·Esko WiltshireDavid R Thorburn
Feb 2, 2008·Brain : a Journal of Neurology·Bernt A EngelsenLaurence A Bindoff
Jun 12, 2008·Human Mutation·Lee-Jun C WongWilliam C Copeland
Sep 3, 2009·Journal of Neuroscience Methods·D J MahadD M Turnbull
Apr 14, 2010·Molecular and Cellular Biology·Ester Perales-ClementeJosé Antonio Enríquez
Jun 26, 2010·Brain : a Journal of Neurology·Kinga TóthZsófia Maglóczky
Jan 13, 2012·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Kalliopi SofouNiklas Darin
Jan 18, 2012·Journal of Neuropathology and Experimental Neurology·Nichola Zoe LaxDouglass Matthew Turnbull
May 12, 2012·Brain : a Journal of Neurology·Nichola Z LaxDoug M Turnbull
Jul 27, 2012·Human Molecular Genetics·Jenni M EloAnu Suomalainen
Feb 20, 2013·Pediatric Neurology·Russell P SanetoRobert K Naviaux
May 21, 2014·Annals of Neurology·Charalampos TzoulisLaurence A Bindoff
Mar 20, 2015·Neuropathology and Applied Neurobiology·Nichola Z LaxDoug M Turnbull
Sep 5, 2015·Neuropathology and Applied Neurobiology·Alexia ChrysostomouNichola Z Lax
Nov 14, 2016·Mitochondrion·Charalampos TzoulisLaurence A Bindoff

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Citations

Apr 28, 2021·Magnetic Resonance Imaging Clinics of North America·Steven P Meyers

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

StereoInvestigator
Volocity
GraphPad Prism

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