Vitamin-responsive epileptic encephalopathies

Vitamin-responsive epileptic encephalopathies P Landrieu CHU Paris Sud hop Bicêtre • Infectious • Malformative • Vascular • Traumatic • Tumoral • …. • Genetic metabolic diseases Early onset epilepsies various causes QuickTime™ et un décompresseur sont requis pour visionner cette image. Crises électriques prolongées Suppression burst Epileptic encephalopathies have a bad prognosis but A small number are accessible to efficient treatment … when given early on. recognizing them is not so difficult ! « Metabolic Diseases » (MD) in clinical pediatrics Monogenic diseases - biochemical marker in body fluids (blood, urine, CSF ) or in tissue (H-MRSpectro) -and/or enzymological marker in accessible cells (leukocytes, fibroblasts, liver, muscle ) Enzymes of intermediary metabolisms - Apoenzyme (protein) - Coenzyme (cofactor): activation of apoenzyme transfer of protons, electrons,various radicals… coenzyme vitamin vitamin modified non-vitaminic cofactor (endogenous synthesis) Coenzyme = vitamin Biotine (B7) coenzyme of carboxylases Acetyl-CoA -, Pyruvate -, propionyl-CoA -, methylcrotonyl-CoA- … Carboxylase Pyridoxine (B6) précursor of pyridoxal-P (coenzyme of transaminases, deaminases, decarboxylases ) Ac panthotenic (B5) precursor of CoA (Coenzyme of acyl-transferases ) coenzyme = modified vitamin Thiamine (B1), precusor of Thiamine-PP (coenzyme of décarboxylases) Cofactors derived from vitamins vitamin Natural form(s) Active forms B1 Thiamine Thiamine-PP B2 Riboflavine FAD Flavine Adénine Dinucléotide FMN Flavine MonoNucleotide B3 (PP) Niacine, Nicotinamide NAD+, NADP+ B5 Panthotenic acid CoA B6 Pyridoxine,pyridoxal,pyridoxamine Pyridoxal-P (PLP) B7-B8 Biotine Biotine B9 Folic A Folinic A, FH4, 5-10CH2FH4, 5CH3FH4… B12 Cobalamin, hydroxycobalamin AdenosylCobalamin, methylCobalamin Non-Vitaminic coenzyme (octanoyl transférase, lipoïl synthase) Octanoïc acid + S Adénosyl Methionine > Lipoïc Acid Coenzyme of: Pyruvate - , 3oxo-glutarate - , branched chain oxo-acid - DH, Glycine cleavage system LA synthetic forms are commercially available [...]... Saccharides, NTP monosaccharide Tetrahydrobiopterin GTP… Electrons, oxygen atom Vitamin-responsive encephalopathies 1 Metabolic Diseases with seizures as the major revealing feature 2 Metabolic Diseases with occasional seizures - MD in period of metab imbalance - MD with multiple neurological symptoms Early-onset epileptic encephalopathies principal forms responsive to vitamin - pyridoxin-dependent convulsions... sont requis pour visionner cette image Vitamin-responsive encephalopathies 1 Metabolic Diseases with seizures as the major revealing feature 2 Metabolic Diseases with occasional seizures - MD in period of metab imbalance - MD with multiple neurological symptoms Acta Paediatr Taiwan 2003 Jul-Aug;44(4):246-8 Maple syrup urine disease presenting with neonatal status epilepticus Wang IJ, Chu SY, Wang CY,... • • • Neonatal onset Etat de mal, polymorph seizures EEG suppresion burst, multifocal spikes Progressive spasticity, deafness, optic atrophy MRI: non-specific signs, cerebral atrophy Resistance to Antiepileptic drugs sensitivity to folinic acid (5mg/kg/day p o) folinic-responsive convulsions • Same biochemical markers than pyridoxin-dependent convulsions – aldehyde α-aminoadipic acid – pipecolic acid . Vitamin-responsive epileptic encephalopathies P Landrieu CHU Paris Sud hop Bicêtre • Infectious • Malformative • Vascular • Traumatic • Tumoral • …. • Genetic. sont requis pour visionner cette image. Crises électriques prolongées Suppression burst Epileptic encephalopathies have a bad prognosis but A small number are accessible to efficient treatment …. sugars Saccharides, NTP monosaccharide Tetrahydrobiopterin GTP… Electrons, oxygen atom Vitamin-responsive encephalopathies 1 Metabolic Diseases with seizures as the major revealing feature 2