epilepsia in boli metabolice [Compatibility Mode]

Afectarea sistemelor de neurotransmitatori
Hiperglicinemie noncetotica
Afectiune metabolica metabolica (blocarea conversiei glicinei glicinei in molecule mai mici);
Debut precoce in perioada neonatala cu letargie, hipotonie, sughit,
oftalmoplegie, tulburari ale functiilor vegetative ale trunchiului cerebral;
evolutia se face spre tetraplegie, retard mental sever
Epilepsia severa severa apare in cursul urmatoarelor luni (initial mioclonii si
crize generalizate, apoi spasme infantile si convulsii partiale motorii
In primele zile EEG arata explozii de varfuri (burst suppression pattern)
care se transforma in activitate lenta cu voltaj mare, si eventual in
hipsaritmie p in j jurul a 3 luni ( (daca copilul p supravietuieste) p ) ( (Applegarth pp g
and Toone 2004).
Diagnostic:
Cresterea concentratiei de glicina in fluide; raport crescut al glicinei in
LCR/plasma (> 0.08);
Scaderea activitatii de degradare hepatica a glicinei; analiza genetica
IRM normal sau agenezie/hipoplazie a corpului calos
Glicina este neurotransmitatorul inhibitor major in maduva si trunchiul
cerebral; se presupune ca simptomatologia initiala este dara de inhibitia
excesiva i l la nivelul i l l acestor t structuri. t t i
Glicina poate actiona si pe post de coactivator al receptorului NMDA
(Thomson 1990).
In hiperglicinemia noncetotica se presupune ca glicina suprasatureaza situl,
ducand la la stiumulare stiumulare excitatorie excitatorie excesiva excesiva si toxicitate postsinaptica
postsinaptica.
Administrarea de benzoat de sodiu (scaderea nivelului glicinei) ar
prelungi supravietuirea. Administrarea de antagonisti NMDA a avut
unele efecte asupra EEG si a convulsiilor (Hamosh et al. 1998).
Copii care supravietuiesc prezinta prezinta epilepsie epilepsie severa. severa Teoretic acidul
valproic trebuie evitat, acesta inhiband suplimentar sistemul de
degradare hepatica a glicinei (Jaeken et al. 1977, MacDermot et al.
1980).
THE GLYCINE CLEAVAGE SYSTEM.
P-protein catalyzes the decarboxylation of
the glycine molecule concomitantly with the
transfer of the residual aminomethyl group
to a sulfur atom on the lipoyl group of the
oxidized H-protein (Hox), generating the
aminomethylated H-protein (Ham).
T-protein catalyzes the transfer of a
methylene group from Ham to
tetrahydrofolate (THF), resulting in the
release of NH3 and the generation of
reduced H-protein (Hred).
The dihydrolipoyl group of Hred is oxidized
by L-protein L protein and the lipoyl group of Hox is
regenerated, thereby completing the
catalytic cycle. (Douce et al, 2001).