Autism: Solving the Puzzle !!! Mostafa Waly, MPH, PhD Assistant Professor Food Science and Nutrition Department College of Agriculture & Marine Sciences Sultan Qaboos University, Oman

Autism Spectrum Disorder: Who? What risk factors? Where? Clinical Picture & Social Impact? Biochemical & Dietary profile? Genetics?

Brain defects in autism

Autistic spectrum disorder (ASD)* Childhood Disintegrative Disorder Pervasive Developmental Disorder Not Otherwise Specified Rett’s Disorder Asperger’s Disorder Autism * Diagnostic criteria (DSM IV & ICD 10) No diagnostic laboratory tests are available

1. Who? Male: female ratio is 3:1 Breastfeeding is a protective factor No clear relation to socio-economic status Onset prior to age 3 years

2. What risk factors? Insults Nutrition & Biochemical abnormalities Infection & Vaccination Environmental Insults Nutrition & Biochemical abnormalities Genetic Predisposition Timing Autism

3. Where? Autism is an epidemic disorder !

Prevalence at the United States

4. Clinical picture & Social Impact Gut Problems Absorptive Difficulties Enzyme Disorders Deficiency Syndromes Poor Detoxification Abilities Immune Reactivity Allergies Poor Blood Flow To The Brain Hippocampus Malfunction Social Impact: Communication Problems Cognitive Difficulties Emotional Disorders Problems With Awareness Poor Eye Contact Behavior Problems Problems with Play Poor Understanding Of Cause and Effect Delayed Development Sleep Problems The DAN approach to treating autism is a biological approach that works hand-in-hand with all the other types of therapies. For those of us who have been involved with DAN, many catchwords keep appearing and reappearing.

5. Biochemical & Dietary profile? Autism Research in Oman: Folate and Vitamin B12. Oxidative Stress and Neuronal Cells Damage. Glutathione (GSH), Intracellular Antioxidant. Reduced Methylation Capacity in Autistic Children. Neurodevelopmental Toxicity and GSH Depletion.

SOURCES OF OXYGEN FREE RADICALS AND CELL INJURY = Oxidative Stress

MECHANISMS OF FREE RADICAL-MEDIATED CELLULAR INJURY Lipid peroxidation – implications for increased permeability in gut and BBB

Antioxidant Defense Counterbalances Oxidative Stress Oxidative Stress Antioxidant Defense Heavy Metals Hydroxyl Radical Hydrogen Peroxide Superoxide Peroxides NO- Superoxide Dismutase GSH Peroxidase GSH Reductase Vitamin E Vitamin C Lipoic Acid GSTs GSH

Cell Death Damage Oxidative Stress Antioxidant Defense Superoxide Dismutase GSH Peroxidase GSH Reductase Vitamin E Vitamin C Lipoic Acid GSTs GSH Heavy Metals Hydroxyl Radical Hydrogen Peroxide Superoxide GSSG Cell Death Damage

Folate and Vitamin B12-dependent HCY- Methionine Cycle

Folate and Vitamin B12 Status Control Children Autistic Children (n=30) (n=30) Serum Folate (µg/l) 6.3 2.1* Serum B12 (pg/ml) 256.8 185.3* Dietary Folate (µg/Day) 240.3 130.1* Diteary B12 (µg/Day) 2.7 1.8* Results are Mean ± SD, * Significantly lower than control children, P<0.05

Oxidative Stress Markers Control Children Autistic Children (n=30) (n=30) Homocysteine , HCY(µmol/l) 13.3 25.7# Glutathione, GSH (µmol/l) 8.4 3.0 * Total Antioxidant Capacity 36.6 11.9* TAC, (mmol/l) Results are Mean ± SD, # Significantly higher than control children, P<0.05 * Significantly lower than control children, P<0.05

6. Genetics? twin studies --- 90%; multiple genes in chromosomes 2 q , 7 q, 16 p, 19 p. Chromosomal anomalies 15 and fragile X syndrome. Recurrence risk studies- siblings of autistic people are more likely to be autistic. Our journey through METHYLCAL SCHOOL begins here with the DAN brochure.

Acknowledgment Dr. Marwan Al-Sharabati, Behavioral Medicine Dept. Dr. Mohammed Al-Shafaee, Family Medicine& Public Health Dept. Dr. Yahya Al-Farsi, Family Medicine& public health Dept. Dr. Amanat Ali, Food Science and Nutrition Dept. Dr. Majeed Al-Ani, Food Science and Nutrition Dept.

They Disserve Our Effort!! شكراً mostafa@squ.edu.om / waly.mostafa@gmail.com I am currently treating between 150 to 200 children with methyl-B12 injections and I receive letters just like these every day!