quand penser à une maladie mitochondriale devant une ... · quand penser à une maladie...
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Quand penser à une maladie
mitochondriale devant une
epilepsie chez l’enfant?
Brigitte Chabrol
Centre de référence, maladies héréditaires du métabolisme
Hôpital d’Enfants, CHU Timone
Marseille, France
Crise épileptique vs Epilepsie
ILAE: 2005
Une crise épileptique est une présence transitoire de signes et/ou
symptômes due à une activité neuronale excessive ou synchrone
anormale dans le cerveau.
L’épilepsie est un trouble cérébral caractérisé:
par une prédisposition durable à générer des crises épileptiques
par les conséquences neurobiologiques, cognitives, psychologiques
et sociales de cette affection.
La définition de l’épilepsie requiert la survenue d’au moins une crise
épileptique.
Enfants épileptiques:
France: 120.000 enfants
40.000 = épilepsie sévère
PACA: 12.000 enfants
4.000 = épilepsie sévère
Combien d’origine mitochondriale ?????
Etude UK: 213 enfants avec épilepsie pharmacorésistante : 2,3 % Mutation POL G (Uusimaa et al, 2013)
Mitochondrial DysfunctioninEpilepsy
DivyaS.Khurana, MD, IgnacioValencia, MD,Michael J.Goldenthal, PhD,
andAgustínLegido, MD, PhD, MBA
Epilepsyisthemostcommonneurologicdisorderworldwideandischaracterizedbyrecurrent
unprovokedseizures.Themitochondrial (mt)respiratorychainisthe nalcommonpathwayfor
cellularenergyproductionthroughtheprocessof oxidativephosphorylation.Asneuronsare
terminallydifferentiatedcellsthatlacksigni cantregenerativecapacityandhaveahighenergy
demand, theyaremorevulnerabletomt dysfunction. Therefore,epilepticseizureshavebeen
welldescribedinseveraldiseasessuchasmtencephalomyopathy, lacticacidosis,andstroke-
like episodes and myoclonic epilepsy and ragged red bers, which are caused by gene
mutationsinmtDNA,amongothers.MutationsinnuclearDNAregulatingmt functionarealso
being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired
epilepsies, whichaccount for about 60%of all epilepsies, isequally important but lesswell
understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of
epilepsyresultingfrommtdysfunctiongraduallydisruptingtheintracellularCa2þ homeostasis,
which modulates neuronal excitability and synaptic transmission, making neurons more
vulnerable toadditional stress, and leading toenergy failureandneuronal loss inepilepsy.
Antiepilepticdrugs(AEDs)alsoaffectmtfunctioninseveralways.Theremustbecautionwhen
treatingepilepsyinpatientswithknownmt disordersassomeAEDsaretoxictothemt.This
reviewsummarizesourcurrentknowledgeoftheeffectofmtdisordersonepilepsy,ofepileptic
seizuresonmt,andofAEDsonmtfunctionandtheimplicationsofall theseinteractionsforthe
management of epilepsyinpatientswithorwithout mt disease.
SeminPediatr Neurol 20:176-187C2013Elsevier Inc.All rightsreserved.
Thedramaticclinical presentationof manyseizuredisor-
derswasdescribedbytheGreekswhodevelopedtheterm
“epilepsy”(meaning“seizedupon”),whichisstillused.1Epileptic
seizureisde nedbytheInternational LeagueAgainst Epilepsy
as “atransient occurrenceof signsand/or symptomsdueto
abnormal excessiveor synchronous neuronal activity in the
brain.”Toestablishthediagnosisof epilepsy, thepatient must
haveat least2nonfebrileseizuresoccurringdaysapartorwithin
24hours.2,3Epilepsyisthemostcommonneurologicdisorder,
affectingabout 0.5%-1.0%of thepopulationworldwide.1-3
Seizuresvary with respect toneurologic involvement and
severity,rangingfromminimalchangesor“staringepisodes”to
orid, generalizedmusclejerkingand lossof consciousness,
which maybelifethreatening.1 Aseizureinvolvesneuronal
dysfunction.Often,therearenostructuralchangesinthebrain
cells. Alternatively, evidence of earlier brain injury, gliosis,
vascular changes, andscarringinbrain tissuemaysuggest a
large-scalestructural problem.1
Theterm“mt disease” referstoanydisorder affectingthe
respiratory chain, or electron transport chain (ETC) and
oxidative phosphorylation (OXPHOS) system to generate
adenosine triphosphate (ATP). This pathway consists of
5multienzymecomplexesoftherespiratorychain(complexes
I-V)containing4 80proteinsandlocatedinthemitochondria
(mt) inner membrane.4-7
Mitochondrial (mt) diseases aremultisystemic disorders.8
However, themost commonclinical presentation isencepha-
lomyopathy, andepilepticseizurescanfrequentlyoccur asan
initial signor manifest duringthecourseof themt encephal-
opathy.9Different epilepsyphenotypeshavebeendescribedin
mt diseases secondary to mtDNA mutations, including mt
encephalomyopathy, lacticacidosis, and stroke-likeepisodes
(MELAS),myoclonicepilepsyandraggedred bers(MERRF),
progressiveexternal ophthalmoplegia, Leber hereditary optic
neuropathy,Kearns-Sayresyndrome,andLeighdisease,among
others.Newepilepsyphenotypesarebeingdescribedassociated
with newmtDNAmutationsand tomt-relatednuclear gene
mutations.3,10 Recently, several authors have reported the
clinicalmanifestationsofepilepsyinpatientswhodemonstrated
176 1071-9091/13/$-seefront matter&2013Elsevier Inc.All rightsreserved.
http://dx.doi.org/10.1016/j.spen.2013.10.001
Sectionof Neurology,Departmentsof PediatricsandNeurology,St. Christo-
pher's Hospital for Children, Drexel University College of Medicine,
Philadelphia, PA.
Addressreprint requeststo DivyaS. Khurana, MD, Section of Neurology,
St.Christopher'sHospital forChildren,3601ASt,Philadelphia,PA19134.
E-mail: divya.khurana@drexelmed.edu
Mitochondrial DysfunctioninEpilepsy
DivyaS.Khurana, MD, IgnacioValencia, MD,Michael J.Goldenthal, PhD,
andAgustínLegido, MD, PhD, MBA
Epilepsyisthemostcommonneurologicdisorderworldwideandischaracterizedbyrecurrent
unprovokedseizures.Themitochondrial (mt)respiratorychainisthe nalcommonpathwayfor
cellularenergyproductionthroughtheprocessof oxidativephosphorylation.Asneuronsare
terminallydifferentiatedcellsthatlacksigni cantregenerativecapacityandhaveahighenergy
demand, theyaremorevulnerabletomt dysfunction. Therefore,epilepticseizureshavebeen
welldescribedinseveraldiseasessuchasmtencephalomyopathy, lacticacidosis,andstroke-
like episodes and myoclonic epilepsy and ragged red bers, which are caused by gene
mutationsinmtDNA,amongothers.MutationsinnuclearDNAregulatingmt functionarealso
being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired
epilepsies, whichaccount for about 60%of all epilepsies, isequally important but lesswell
understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of
epilepsyresultingfrommtdysfunctiongraduallydisruptingtheintracellularCa2þ homeostasis,
which modulates neuronal excitability and synaptic transmission, making neurons more
vulnerable toadditional stress, and leading toenergy failureandneuronal loss inepilepsy.
Antiepilepticdrugs(AEDs)alsoaffectmtfunctioninseveralways.Theremustbecautionwhen
treatingepilepsyinpatientswithknownmt disordersassomeAEDsaretoxictothemt.This
reviewsummarizesourcurrentknowledgeoftheeffectofmtdisordersonepilepsy,ofepileptic
seizuresonmt,andofAEDsonmtfunctionandtheimplicationsofall theseinteractionsforthe
management of epilepsyinpatientswithorwithout mt disease.
SeminPediatr Neurol 20:176-187C2013Elsevier Inc.All rightsreserved.
Thedramaticclinical presentationof manyseizuredisor-
derswasdescribedbytheGreekswhodevelopedtheterm
“epilepsy”(meaning“seizedupon”),whichisstillused.1Epileptic
seizureisde nedbytheInternational LeagueAgainst Epilepsy
as “atransient occurrenceof signsand/or symptomsdueto
abnormal excessiveor synchronous neuronal activity in the
brain.”Toestablishthediagnosisof epilepsy, thepatient must
haveat least2nonfebrileseizuresoccurringdaysapartorwithin
24hours.2,3Epilepsyisthemostcommonneurologicdisorder,
affectingabout 0.5%-1.0%of thepopulationworldwide.1-3
Seizuresvary with respect toneurologic involvement and
severity,rangingfromminimalchangesor“staringepisodes”to
orid, generalizedmusclejerkingand lossof consciousness,
which maybelifethreatening.1 Aseizureinvolvesneuronal
dysfunction.Often,therearenostructuralchangesinthebrain
cells. Alternatively, evidence of earlier brain injury, gliosis,
vascular changes, andscarringinbrain tissuemaysuggest a
large-scalestructural problem.1
Theterm“mt disease” referstoanydisorder affectingthe
respiratory chain, or electron transport chain (ETC) and
oxidative phosphorylation (OXPHOS) system to generate
adenosine triphosphate (ATP). This pathway consists of
5multienzymecomplexesoftherespiratorychain(complexes
I-V)containing4 80proteinsandlocatedinthemitochondria
(mt) inner membrane.4-7
Mitochondrial (mt) diseases aremultisystemic disorders.8
However, themost commonclinical presentation isencepha-
lomyopathy, andepilepticseizurescanfrequentlyoccur asan
initial signor manifest duringthecourseof themt encephal-
opathy.9Different epilepsyphenotypeshavebeendescribedin
mt diseases secondary to mtDNA mutations, including mt
encephalomyopathy, lacticacidosis, and stroke-likeepisodes
(MELAS),myoclonicepilepsyandraggedred bers(MERRF),
progressiveexternal ophthalmoplegia, Leber hereditary optic
neuropathy,Kearns-Sayresyndrome,andLeighdisease,among
others.Newepilepsyphenotypesarebeingdescribedassociated
with newmtDNAmutationsand tomt-relatednuclear gene
mutations.3,10 Recently, several authors have reported the
clinicalmanifestationsofepilepsyinpatientswhodemonstrated
176 1071-9091/13/$-seefront matter&2013Elsevier Inc.All rightsreserved.
http://dx.doi.org/10.1016/j.spen.2013.10.001
Sectionof Neurology,Departmentsof PediatricsandNeurology,St. Christo-
pher's Hospital for Children, Drexel University College of Medicine,
Philadelphia, PA.
Addressreprint requeststo DivyaS. Khurana, MD, Section of Neurology,
St.Christopher'sHospital forChildren,3601ASt,Philadelphia,PA19134.
E-mail: divya.khurana@drexelmed.edu
Mitochondrial DysfunctioninEpilepsy
DivyaS.Khurana, MD, IgnacioValencia, MD,Michael J.Goldenthal, PhD,
andAgustínLegido, MD, PhD, MBA
Epilepsyisthemostcommonneurologicdisorderworldwideandischaracterizedbyrecurrent
unprovokedseizures.Themitochondrial (mt)respiratorychainisthe nalcommonpathwayfor
cellularenergyproductionthroughtheprocessof oxidativephosphorylation.Asneuronsare
terminallydifferentiatedcellsthatlacksigni cantregenerativecapacityandhaveahighenergy
demand, theyaremorevulnerabletomt dysfunction. Therefore,epilepticseizureshavebeen
welldescribedinseveraldiseasessuchasmtencephalomyopathy, lacticacidosis,andstroke-
like episodes and myoclonic epilepsy and ragged red bers, which are caused by gene
mutationsinmtDNA,amongothers.MutationsinnuclearDNAregulatingmt functionarealso
being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired
epilepsies, whichaccount for about 60%of all epilepsies, isequally important but lesswell
understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of
epilepsyresultingfrommtdysfunctiongraduallydisruptingtheintracellularCa2þ homeostasis,
which modulates neuronal excitability and synaptic transmission, making neurons more
vulnerable toadditional stress, and leading toenergy failureandneuronal loss inepilepsy.
Antiepilepticdrugs(AEDs)alsoaffectmtfunctioninseveralways.Theremustbecautionwhen
treatingepilepsyinpatientswithknownmt disordersassomeAEDsaretoxictothemt.This
reviewsummarizesourcurrentknowledgeoftheeffectofmtdisordersonepilepsy,ofepileptic
seizuresonmt,andofAEDsonmtfunctionandtheimplicationsofall theseinteractionsforthe
management of epilepsyinpatientswithorwithout mt disease.
SeminPediatr Neurol 20:176-187C2013Elsevier Inc.All rightsreserved.
Thedramaticclinical presentationof manyseizuredisor-
derswasdescribedbytheGreekswhodevelopedtheterm
“epilepsy”(meaning“seizedupon”),whichisstillused.1Epileptic
seizureisde nedbytheInternational LeagueAgainst Epilepsy
as “atransient occurrenceof signsand/or symptomsdueto
abnormal excessiveor synchronous neuronal activity in the
brain.”Toestablishthediagnosisof epilepsy, thepatient must
haveat least2nonfebrileseizuresoccurringdaysapartorwithin
24hours.2,3Epilepsyisthemostcommonneurologicdisorder,
affectingabout 0.5%-1.0%of thepopulationworldwide.1-3
Seizuresvary with respect toneurologic involvement and
severity,rangingfromminimalchangesor“staringepisodes”to
orid, generalizedmusclejerkingand lossof consciousness,
which maybelifethreatening.1 Aseizureinvolvesneuronal
dysfunction.Often,therearenostructuralchangesinthebrain
cells. Alternatively, evidence of earlier brain injury, gliosis,
vascular changes, andscarringinbrain tissuemaysuggest a
large-scalestructural problem.1
Theterm“mt disease” referstoanydisorder affectingthe
respiratory chain, or electron transport chain (ETC) and
oxidative phosphorylation (OXPHOS) system to generate
adenosine triphosphate (ATP). This pathway consists of
5multienzymecomplexesoftherespiratorychain(complexes
I-V)containing4 80proteinsandlocatedinthemitochondria
(mt) inner membrane.4-7
Mitochondrial (mt) diseases aremultisystemic disorders.8
However, themost commonclinical presentation isencepha-
lomyopathy, andepilepticseizurescanfrequentlyoccur asan
initial signor manifest duringthecourseof themt encephal-
opathy.9Different epilepsyphenotypeshavebeendescribedin
mt diseases secondary to mtDNA mutations, including mt
encephalomyopathy, lacticacidosis, and stroke-likeepisodes
(MELAS),myoclonicepilepsyandraggedred bers(MERRF),
progressiveexternal ophthalmoplegia, Leber hereditary optic
neuropathy,Kearns-Sayresyndrome,andLeighdisease,among
others.Newepilepsyphenotypesarebeingdescribedassociated
with newmtDNAmutationsand tomt-relatednuclear gene
mutations.3,10 Recently, several authors have reported the
clinicalmanifestationsofepilepsyinpatientswhodemonstrated
176 1071-9091/13/$-seefront matter&2013Elsevier Inc.All rightsreserved.
http://dx.doi.org/10.1016/j.spen.2013.10.001
Sectionof Neurology,Departmentsof PediatricsandNeurology,St. Christo-
pher's Hospital for Children, Drexel University College of Medicine,
Philadelphia, PA.
Addressreprint requeststo DivyaS. Khurana, MD, Section of Neurology,
St.Christopher'sHospital forChildren,3601ASt,Philadelphia,PA19134.
E-mail: divya.khurana@drexelmed.edu
Mitochondrial DysfunctioninEpilepsy
DivyaS.Khurana, MD, IgnacioValencia, MD,Michael J.Goldenthal, PhD,
andAgustínLegido, MD, PhD, MBA
Epilepsyisthemostcommonneurologicdisorderworldwideandischaracterizedbyrecurrent
unprovokedseizures.Themitochondrial (mt)respiratorychainisthe nalcommonpathwayfor
cellularenergyproductionthroughtheprocessof oxidativephosphorylation.Asneuronsare
terminallydifferentiatedcellsthatlacksigni cantregenerativecapacityandhaveahighenergy
demand, theyaremorevulnerabletomt dysfunction. Therefore,epilepticseizureshavebeen
welldescribedinseveraldiseasessuchasmtencephalomyopathy, lacticacidosis,andstroke-
like episodes and myoclonic epilepsy and ragged red bers, which are caused by gene
mutationsinmtDNA,amongothers.MutationsinnuclearDNAregulatingmt functionarealso
being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired
epilepsies, whichaccount for about 60%of all epilepsies, isequally important but lesswell
understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of
epilepsyresultingfrommtdysfunctiongraduallydisruptingtheintracellularCa2þ homeostasis,
which modulates neuronal excitability and synaptic transmission, making neurons more
vulnerable toadditional stress, and leading toenergy failureandneuronal loss inepilepsy.
Antiepilepticdrugs(AEDs)alsoaffectmtfunctioninseveralways.Theremustbecautionwhen
treatingepilepsyinpatientswithknownmt disordersassomeAEDsaretoxictothemt.This
reviewsummarizesourcurrentknowledgeoftheeffectofmtdisordersonepilepsy,ofepileptic
seizuresonmt,andofAEDsonmtfunctionandtheimplicationsofall theseinteractionsforthe
management of epilepsyinpatientswithorwithout mt disease.
SeminPediatr Neurol 20:176-187C2013Elsevier Inc.All rightsreserved.
Thedramaticclinical presentationof manyseizuredisor-
derswasdescribedbytheGreekswhodevelopedtheterm
“epilepsy”(meaning“seizedupon”),whichisstillused.1Epileptic
seizureisde nedbytheInternational LeagueAgainst Epilepsy
as “atransient occurrenceof signsand/or symptomsdueto
abnormal excessiveor synchronous neuronal activity in the
brain.”Toestablishthediagnosisof epilepsy, thepatient must
haveat least2nonfebrileseizuresoccurringdaysapartorwithin
24hours.2,3Epilepsyisthemostcommonneurologicdisorder,
affectingabout 0.5%-1.0%of thepopulationworldwide.1-3
Seizuresvary with respect toneurologic involvement and
severity,rangingfromminimalchangesor“staringepisodes”to
orid, generalizedmusclejerkingand lossof consciousness,
which maybelifethreatening.1 Aseizureinvolvesneuronal
dysfunction.Often,therearenostructuralchangesinthebrain
cells. Alternatively, evidence of earlier brain injury, gliosis,
vascular changes, andscarringinbrain tissuemaysuggest a
large-scalestructural problem.1
Theterm“mt disease” referstoanydisorder affectingthe
respiratory chain, or electron transport chain (ETC) and
oxidative phosphorylation (OXPHOS) system to generate
adenosine triphosphate (ATP). This pathway consists of
5multienzymecomplexesoftherespiratorychain(complexes
I-V)containing4 80proteinsandlocatedinthemitochondria
(mt) inner membrane.4-7
Mitochondrial (mt) diseases aremultisystemic disorders.8
However, themost commonclinical presentation isencepha-
lomyopathy, andepilepticseizurescanfrequentlyoccur asan
initial signor manifest duringthecourseof themt encephal-
opathy.9Different epilepsyphenotypeshavebeendescribedin
mt diseases secondary to mtDNA mutations, including mt
encephalomyopathy, lacticacidosis, and stroke-likeepisodes
(MELAS),myoclonicepilepsyandraggedred bers(MERRF),
progressiveexternal ophthalmoplegia, Leber hereditary optic
neuropathy,Kearns-Sayresyndrome,andLeighdisease,among
others.Newepilepsyphenotypesarebeingdescribedassociated
with newmtDNAmutationsand tomt-relatednuclear gene
mutations.3,10 Recently, several authors have reported the
clinicalmanifestationsofepilepsyinpatientswhodemonstrated
176 1071-9091/13/$-seefront matter&2013Elsevier Inc.All rightsreserved.
http://dx.doi.org/10.1016/j.spen.2013.10.001
Sectionof Neurology,Departmentsof PediatricsandNeurology,St. Christo-
pher's Hospital for Children, Drexel University College of Medicine,
Philadelphia, PA.
Addressreprint requeststo DivyaS. Khurana, MD, Section of Neurology,
St.Christopher'sHospital forChildren,3601ASt,Philadelphia,PA19134.
E-mail: divya.khurana@drexelmed.edu
Cause ou conséquence ????
Cause ou conséquence ????
Role du stress oxydatif :
Modification de l’excitabilité
synaptique, et de la transmission synaptique ,
Entrainant une plus grande
vulnérabilité neuronale
Déficit énérgetique secondaire
Perte neuronale
Cause ou conséquence ????
Chez le rat, induction état de mal temporal par acide kainique deficits en complexes I et 3 observés à H3
Chez des patients avec epilepsie temporale et sclérose de l’hippocampe : anomalies ultrastrucurales des mitochondries, et déficit de la chaiîne respiratoire, surtout du complexe 1 ,dans la région C1 de l’hippocampe mais pas dans le reste du tissu cérébral
Atteinte spécifique du complexe 1=
témoin de la mort neuronale induite par les crises
rôle crucial dans l’épileptogénèse
56 patients (1990-2006)
Autres signes précédant l’épilepsie dans 82, 5 % des cas :
Retard de croissance,
Anomalies du développement psychomoteur
Ataxie
Atteinte multisystémique
60 % des patients répartis en 6 groupes
Etat de mal dans le cadre d’une atteinte néonatale multiviscérale (2 patients),
Encéphalopathie myoclonqique néonatale ( 3 patients)
Spasmes infantiles(8 patients),
Etat de mal réfractaire ou récurrent (21 patients),
Epilepsie partielle continue (4 patients),
Epilpesie myoclonique (18 patients).
Epilepsie difficile à traiter dans 95% des cas
Valproate : 25 patients, un seul insuffisance hépatique aigue à J6.
Epilepsie = facteur pronostique sevère: 45% décès, ( la moitié dans les 9 mois aprés le début de l’Epilespie)
Intêret de la PBH
1995 et 2010: 53 enfants épileptiques
groupe 1: présence d’un dysfonctionnement de la
chaîne respiratoire mitochondriale
groupe 2: absence de pathologie mitochondriale.
Archives de Pédiatrie 2012;19:794-802
En pratique :
Epilepsie : trés rarement signe inaugural et isolé
Nombreuses autres atteintes d’organes:
Retard de croissance ( parfois anténatal)
Anomalies du développement psychomoteur
Ophtalmologiques à type d’apraxie oculomotrice, atrophie
optique, rétinite pigmentaire
Auditives: surdité , hypo-acousie
Hépatiques: cytolyse, hépatomégalie
Atteinte plurisystémique ++++++
En pratique: EEG
Pas de tracés pathognomoniques
( contrairement à NCL 2)
En pratique:
IRM +SRM : anomalies chez + de 90 %
Atteinte corticale, ,
Atteinte cérébelleuse
Atteinte des noyaux gris
Atteinte de la SB
en SRM, pic de lactates
Exceptionellement normal
En pratique:
Pas de corrélation nette entre le type d’epilepsie et
le déficit de la chaine respiratoire mitochondriale
Intêret de la PBH
Nombreuses mutations nucléaires +++ ou DNAmt
Tout n’est pas mitochondrial
Encéphalopathies épileptiques précoces :
2 gènes dominants majeurs fréquents :
STXBP1 et KCNQ2
2 gènes récessifs avec une clinique particulière :
TBC1D24 et SLC13A5
XXX autres gènes : CDKL5, PIGQ, PIGO, SCN2A,GNAO1, KCNT1, SLC25A22, PNKP, PLCB1, DOCK7, SLC35A2, GABRB3, HDAC4, SCN8A, SPTAN1, GRIN2A, GRIN2B…
EMP
Ohtahara
Dr Martine Gavaret- CINAPSE
Service de réanimation néonatale. La conception.
Tout n’est pas mitochondrial
STXBP1 KCNQ2
Age début 0-6 semaines 1ere semaine
Type Orage / crises
focales
Orage de crises
toniques
EEG SB / focal SB
Evolution de
l’épilepsie
Rémission Rémission
Evolution EEG Rythmes rapides Anomalies
« fonctionnelles »
PC Normal Normal
Mouvements
anormaux
+++ ++
KCNQ2 (46 cas publiés)
STXBP1 (40 cas)
0
5
10
15
20
25
30
35
40
45
50
0,5 1 2 3 4 5 6 >6
Déficit chaîne respiratoire parfois retrouvé:= secondaire
Tout n’est pas mitochondrial
Mutation RANBP2: Encephalopathie aigue nécrosante
Tout n’est pas mitochondrial
1er enfant: décés à 9 mois: état de mal fébrile,
défaillance multiviscérale en 1 semaine
2eme enfant tableau identique à 9 mois, séquelles
majeures, décès à 3 ans
3eme enfant même tableau à 9 mois,
Etat de mal épileptique
Atteinte hepatique sévère
Coma
Deficit complexe 5
Actuellement: Retard mental, Epilepsie partielle
Au total:
Maladie mitochondriale rarement cause d’une épilepsie
Epilepsie sévère fréquente au cours des maladies
mitochondriales ( 30 %)
Chez l’enfant, epilepsie généralisée
Chez adulte: épilespie partielle
Facteur de mauvais pronostic
Equipe pluridiisciplinaire indispensable = neuropédiatre,
métabolicien, généticien , biochimiste…..
Au total
Pluridisciplinarité=
Filière Maladies Héréditaires du Métabolisme
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