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Tapan Audhya, PhDNew York University, NY & Vitamin Diagnostics, NJ
Autism One 2009 Conference
Chicago, IL.
May, 2009
Unprovoked Seizures in Autistic Individuals
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Seizure (Sudden, Abnormal electrical activity in brain)
Partial seizure (Focal, sensory or petit mal)(one part of brain; particularly the site which directs “flight” response; conscious; either tonic or clonic)
Generalized seizure
(Both site of brain)
Unconscious; Both tonic and clonic
Simple
(No loss of consciousness)Complex
Epilepsy – a recurrent seizure
Non-epileptic Seizure – Similar to epileptic.
Seizure but not caused by electrical disruption of cerebral cortex. Classified as 1) physiologic or 2) psychogenic
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Nutritional Status of Autistic Nutritional Status of Autistic Children with SeizureChildren with Seizure
Age Group
4 -16 years ; N = 89 (Boys - 66, Girls – 23)
Repetitive Epileptic Seizure
1-7.2 min (mean – 4.0 min)
3 - 4 times a day
ICD-9 → 345.4;345.9;343.4;299.0
Epileptic Seizure was confirmed by EEG on29 boys and 5 girls
17 children had spinal tap for unrelated reason
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Vitamin B1 in Plasma
32 low, 57 normal
Vitamin B6 in Plasma
30 low, 40 high, 44 low in P-5-P
Biotin in Plasma
23 low, 43 normal
These children were also hypoglycemic
Folic Acid in Plasma
Low only in those children who take anticonvulsant medication. 11 children had problem with impaired transport of folate across the BBB. 8/14 low in CSF
Vitamin E in Plasma
45 low, 2 high, 42 normal
Vitamin D in Plasma
27 low in D3;
(all of them had anticonvulsant medication)
Minerals
Magnesium
39 low in plasma
19 low in RBC
10 low in WBC
10/17 low in CSF
Selenium
8/17 low in CSF
20 low in Plasma
Manganese
32 low in plasma & RBC
Calcium
10/17 high in CSF
16 low in Plasma
5 high in RBC
Vitamins & Minerals
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Protein & Amino AcidsProtein & Amino Acids
ProlactinProlactin 199 amino acid, Hypothalamic peptide & controlled 199 amino acid, Hypothalamic peptide & controlled
by Dopamineby Dopamine21 boys and 3 girls had high plasma prolactin 21 boys and 3 girls had high plasma prolactin
(2 -3x the normal levels)(2 -3x the normal levels)11 boys & 3 girls had low Dopamine11 boys & 3 girls had low Dopamine
GlutamateGlutamate 14/17 high glutamate in CSF, 42 high in Plasma14/17 high glutamate in CSF, 42 high in Plasma
AspertateAspertate 14 high in Plasma & CSF14 high in Plasma & CSF
TaurineTaurine 10/17 low in CSF, 34 low in Plasma10/17 low in CSF, 34 low in Plasma
GABAGABA 13/17 low in CSF, 28 high in Plasma, 59 low in Plasma13/17 low in CSF, 28 high in Plasma, 59 low in Plasma
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Synthesis of GABA and Synthesis of GABA and αα--KetoglutarateKetoglutarate
Glutamine → Glutamate
Decarboxylase GABA P-5-P
Transaminase
P-5-Pα-Ketoglutarate
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Glutathione PeroxidaseGlutathione Peroxidase
26 low normal26 low normal
34 less than half the normal value34 less than half the normal value
H202
H20 + 02
Glutathione Peroxidase (GP)
GSH GSSGGP
GR
SOD
Free Radical Oxygen
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Autism, Seizure & Neurotransmitters Autism, Seizure & Neurotransmitters (NT)(NT)
NTs are chemicals that transfer information from one neuron to another
NTs have two basic functions
• Inform receiving neuron to “Fire” Excitatory
• Inform receiving neuron to stop “Firing” Inhibitory
These actions of NTs depend on a class of proteins which is known as receptors.
These receptors initiate the activity after receiving the NTs.
GABA, for example, binds to receptors which are inhibitory.
Most anti anxiety medications increase GABA transmission More GABA receptor activation Shut down the CNS Relaxation
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GABA Receptor
GABAergic system in cerebellum and limbic structure in affected in autism. Inhibition of this system is suppressed by
1. Impairment of GABA-receptor
2. Antagonism of GABAergic neurons bearing receptors sensitive to glutamate analog NMDA.
Example:
Pathology relating to GABA receptors and suspected etiologies of autism
Excessive glutamate activation of non-NMDA glutamate receptor – Pathology observed in Autism
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GABA Receptor submit Genes in AutismGABA Receptor submit Genes in AutismChromosomeChromosome GABA-receptor GABA-receptor
Subunit GeneSubunit Gene4p124p12 GABRG1GABRG1
-A2-A2
-A4-A4
-B1 -B1
5q345q34 -B2-B2
-A6-A6
-A1-A1
-G2-G2
-P-P
6q156q15 -R1-R1
-R2-R2
15q1215q12 -A5-A5
-B3-B3
-G3-G3
Only GABR A4 is involved in the etiology of autism and gene – gene interaction between GABR A4 and GABR B1
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GABAGABAAA Receptor Receptor
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GABAGABAAA Receptor Receptor
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Controlling Seizures by Nutritional ApproachControlling Seizures by Nutritional ApproachKetogenic Diet : A diet high in fats, low in protein and carbohydrate.
Fat: (carb + protein) = 4:1
However, never make too low carb (Hypoglycemia) Medium chain Triglycerides (MCT) are more ketogenic.
TaurineTaurine 500 mg/day; 500 mg/day; divided in divided in
3 batches 3 batches
Vit – BVit – B11 20 mg/day 20 mg/day
Folic AcidFolic Acid 400 mcg/day 400 mcg/day Vit – BVit – B1212 200 mcg/day 200 mcg/day
Vit BVit B66 20 mg/kg Body wt. 20 mg/kg Body wt. Mg Mg 400 mg/day 400 mg/day
Mn Mn 5 mg/day 5 mg/day ZnZn 20 mg/day 20 mg/day
DMGDMG 100 mg/day 100 mg/day SeSe 100 mcg/day 100 mcg/day
L-CarnitineL-Carnitine 100 mg/day 100 mg/day Vit. E (natural)Vit. E (natural) 100 mg/day 100 mg/day
L-carnosineL-carnosine 250 mg/2 x day 250 mg/2 x day