boala leigh

8/15/2019 Boala Leigh

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Sindrom Leigh –Feigin -Wolf(Encefalopatie necrozantasubacuta)

Realizat Sin!ereanu"ade!da

#r$ %&'

Universitatea de Stat de Medicina si Farmacie

“Nicolae Testemitanu” din Republica Moldova


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finiti :

Boala Leigh este o afec iunețereditară rară care afectează sistemul

nervos central . Este numit dupăArchibald Denis Leigh (1915199!"# un

neuropsihiatru britanic #care primul

a descris starea $n 1951. %oala aparede obicei $n primul an de via ă.ț

https://en.wikipedia.org/wiki/Central_nervous_systemhttps://en.wikipedia.org/wiki/Central_nervous_systemhttps://en.wikipedia.org/wiki/Central_nervous_systemhttps://en.wikipedia.org/wiki/Central_nervous_system


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Fenotipul in BoalaLeigh:

%oala Leigh se manifesta prin&'ierderea progresivă a abilită ilor mentaleț

i de circula ie (psihomotorii de regresie"ș țipotonieDistonie

Ata)ie*urditate +europatie periferica


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*auza bolii

Sindromul Leigh poate ! cau"ata de mutatii intr# una din peste $% de gene di&erite'

Intre 20 si 25 la suta din cazurile sindromului Leighsunt mutatii in ADN - ul mitocondrial. Cele mai

frecvente dintre aceste mutatii se gaseste de la0!ana la 20 la suta din sindromul Leigh si a!are lamutatia genei "#-A#$% & o gen' care codi(c' o!rotein' din ultimul com!le) al lan*ului de fosforilareo)idativ& A#$ - sintaza & o enzim' care genereaz' +n

mod direct de A#$. ,'r' a A#$ - sintaza& lan*ulde trans!ort de electroni nu va !roduce nici A#$.

Cele mai frecvente mutatie "#-A#$% gasit cu sindromLeigh este o muta*ie !unctual' la nucleotida

/1 & care se schim' o timin' la un guanin'.

https://en.wikipedia.org/wiki/MT-ATP6https://en.wikipedia.org/wiki/ATP_synthasehttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/Point_mutationhttps://en.wikipedia.org/wiki/Thyminehttps://en.wikipedia.org/wiki/Guaninehttps://en.wikipedia.org/wiki/Guaninehttps://en.wikipedia.org/wiki/Thyminehttps://en.wikipedia.org/wiki/Point_mutationhttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/ATP_synthasehttps://en.wikipedia.org/wiki/MT-ATP6


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Început:/523 aze !erechi

Sfârşit:203 aze !erechiDimensiune:

%/ aze

#ena responsabila

4ena "#-A#$%este situat +nADN-ul mitocondrial


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(articularit)*ile genei mitocondriale


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Functiile genei

La nivel de moleculă Codifică sinteza Proteinei MT-

ATP6;

La nivel de celulă

Proteina MT-ATP6 este

responsabila de producereaATP (adenozin trifosfat)

principala sursa de ener!ie dincelulă"

La nivel de or!anism

#ealizează transportul deener!ie prin tot corpul

omenesc"


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+roteina

(roteina MT#+T(, cunoscut su numelede comple- . &este res!onsail !entru eta!a (nal' a

fosforil'rii o)idative."ai e)act& un segment de A#$ sintetaza

!ermite incarcarea !ozitiva a !articulelor de$rotoni !entru a curge !rintr-o memran's!ecial' +n interiorul mitocondriei.

n al doilea segment al A#$ sintetazeifoloseste energia&care a fost creata de acest

val de !rotoni !entru a forma o molecul'AD6N78IN DI,79,A#:AD$; de A#$.


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/imensiune: ,aminoaciziMasa molecular): .&/

0a


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*onsecintele mutatiei

La nivel molecular: blochează generarea de

ATP.La nivel celular: reduce activitatea altor

complexe de proteine de fosforilare oxidativă

sau conduce la reducerea sintezei de proteine

mitocondriale, toate care afectează produc iaț

de energie mitocondriale.La nivel de organism: Moartea celulelor din

creier, cauzele leziunilor caracteristice observate

n sindromul Leigh


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Tabloul constituit are aspect deence&alopatie progresiva 0 regresulachi"itiilor psihomotorii:

crize convulsive hi!otonie

semne !iramidale atro(e o!tica& cecitate&nistagmus

tremor intentional& ata)ie&!aralizii de nerv III& I


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Freventa:

9indromul Leigh afecteaza cel !utin la =0.000 de nou - n'scu*i. Conditie

este mai frecventa in anumite!o!ulatii.De e)em!lu& condi*ia a!are la

a!ro)imativ din 2000 de nou - n'scu*i +n

regiunea 9aguena> Lac-9aint-?eandin @ueec& Canada.


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/iagnostic:,linic& studii biochimice a in sange creste nivelul de& lactat#

piruvat# alanina-

in urina creste & alanina# acidurie fumarica-

in L, creste & lactatul# piruvatul-

Determinari enzimatice & in urina# sange# L,# in culturi defibroblasti cutanati si muschi# dozarea endorfinelor si

noradrenalinei in L,.

• /enetic& analiza ',#

analiza L0's a genei 2A2'3 secventierea genei 2A2'3

olecular& analizarae moleculara si functionala a sistemelor in

parte ,24 + cerebrala

E)amen instrumental&*/# EE/# E,/# raze 6# laser.


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Solutii de prevenire :

Diagnosticul genetic preconceptual al parintilor.E)cluderea factorilor mutageni e)terni &

deprinderi nocive# conditii nefavorabilede munca si trai.

Diagnosticarea prenatala & studiul

activitatii enzimatice la nivelulvilozitatilor coriale prelevate prin biopsie

sfatul genetic


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Solutii de terapie etiologica

* regim alimentar:• glutamina sarac in hidrati de carbon bogat in grasimi tiamina in doze mari acid lipoic

* tratament simptomatic• Coenzima Q10

Studiile clinice ale medicamentului EPI-7! pentru

boala "eigh sunt #n curs de des$% urare&ș


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Bibliogra!e:

htt!sBBghr.nlm.nih.govBconditionBleigh-s>ndromesourcesfor!age

htt!sBBen.iEi!edia.orgBiEiBLeighFdisease"itochondrialFDNAFmutations

http11222$nobelprize$org1nobel3priz

es1chemistr41laureates1&55/1press$html

htt!BB.romedic.roBsindrom-mils-sindrom-leig

h-mostenit-!e-cale-materna
https://ghr.nlm.nih.gov/condition/leigh-syndromehttps://ghr.nlm.nih.gov/condition/leigh-syndromehttps://ghr.nlm.nih.gov/condition/leigh-syndromehttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/Leigh_diseasehttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.romedic.ro/sindrom-mils-sindrom-leigh-mostenit-pe-cale-maternahttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttp://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/press.htmlhttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/Leigh_diseasehttps://en.wikipedia.org/wiki/Leigh_diseasehttps://ghr.nlm.nih.gov/condition/leigh-syndromehttps://ghr.nlm.nih.gov/condition/leigh-syndromehttps://ghr.nlm.nih.gov/condition/leigh-syndrome

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