Autism: Solving the Puzzle !!! Mostafa Waly , MPH, PhD Assistant Professor
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Autism: Solving the Puzzle !!!Autism: Solving the Puzzle !!!
Mostafa Waly, MPH, PhDMostafa Waly, MPH, PhD
Assistant ProfessorAssistant Professor
Food Science and Nutrition DepartmentFood Science and Nutrition Department
College of Agriculture & Marine SciencesCollege of Agriculture & Marine Sciences
Sultan Qaboos University, OmanSultan Qaboos University, Oman
Autism Spectrum Disorder:Autism Spectrum Disorder:
1.1. Who?Who?
2.2. What risk factors?What risk factors?
3.3. Where?Where?
4.4. Clinical Picture & Social Clinical Picture & Social Impact?Impact?
5.5. Biochemical & Dietary Biochemical & Dietary profile?profile?
6.6. Genetics?Genetics?
Brain defects in autismBrain defects in autism
Autistic spectrum disorder Autistic spectrum disorder (ASD)*(ASD)*
Autism Rett’s Disorder
Asperger’s Disorder
Childhood
Disintegrative
Disorder
Pervasive Developmental Disorder Not Otherwise Specified
• * Diagnostic criteria (DSM IV & ICD 10)* Diagnostic criteria (DSM IV & ICD 10)• No diagnostic laboratory tests are availableNo diagnostic laboratory tests are available
1. Who?1. Who?
• Male: female ratio is 3:1 Male: female ratio is 3:1
• Breastfeeding is a protective factor Breastfeeding is a protective factor
• No clear relation to socio-economic No clear relation to socio-economic statusstatus
• Onset prior to age 3 yearsOnset prior to age 3 years
Infection & VaccinationEnvironmental
Insults
Nutrition&
Biochemicalabnormalities
GeneticPredisposition
Timing Autism
2. What risk factors?2. What risk factors?
3. Where?3. Where?Autism is an epidemic disorder !Autism is an epidemic disorder !
Prevalence at the United StatesPrevalence at the United States
• 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
Clinical Picture:•Gut Problems •Absorptive Difficulties •Enzyme Disorders•Deficiency Syndromes •Poor Detoxification Abilities•Immune Reactivity •Allergies•Poor Blood Flow To The Brain•Hippocampus Malfunction
4. Clinical picture & Social 4. Clinical picture & Social ImpactImpact
• 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.
5. Biochemical & Dietary 5. Biochemical & Dietary profile?profile?
SOURCES OF OXYGEN FREE RADICALS AND CELL INJURY
= Oxidative Stress
MECHANISMS OF FREE RADICAL-MEDIATED CELLULAR INJURY
Oxidative Stress Antioxidant Defense
Superoxide DismutaseGSH Peroxidase
GSH ReductaseVitamin EVitamin CLipoic Acid
GSTsGSH
Heavy MetalsHydroxyl Radical
Hydrogen PeroxideSuperoxidePeroxides
NO-
Antioxidant Defense Counterbalances Oxidative Stress
Oxidative Stress Antioxidant Defense
Superoxide DismutaseGSH PeroxidaseGSH Reductase
Vitamin EVitamin CLipoic Acid
GSTsGSH
Heavy MetalsHydroxyl Radical
Hydrogen PeroxideSuperoxide
GSSG
Cell DeathDamage
Folate and Vitamin B12-dependent HCY- Methionine Cycle
Folate and Vitamin B12 Status
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*
Control Children Autistic Children (n=30) (n=30)
Results are Mean ± SD, * Significantly lower than control children, P<0.05
Oxidative Stress Markers
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)
Control Children Autistic Children (n=30) (n=30)
Results are Mean ± SD, # Significantly higher than control children, P<0.05* Significantly lower than control children, P<0.05
6. Genetics?6. Genetics?
twin studies --- 90%; multiple genes twin studies --- 90%; multiple genes inin
chromosomes 2 q , 7 q, 16 p, 19 p.chromosomes 2 q , 7 q, 16 p, 19 p.
Chromosomal anomalies 15 and Chromosomal anomalies 15 and fragile X syndrome. fragile X syndrome.
Recurrence risk studies- siblings of Recurrence risk studies- siblings of autistic people are more likely to be autistic people are more likely to be autistic.autistic.
AcknowledgmentAcknowledgment
Dr. Marwan Al-Sharabati, Dr. Marwan Al-Sharabati, Behavioral Medicine Dept.Behavioral Medicine Dept.
Dr. Mohammed Al-Shafaee, Dr. Mohammed Al-Shafaee, Family Medicine& Public Health Family Medicine& Public Health Dept.Dept.
Dr. Yahya Al-Farsi, Dr. Yahya Al-Farsi, Family Medicine& public health Dept.Family Medicine& public health Dept.
Dr. Amanat Ali, Dr. Amanat Ali, Food Science and Nutrition Dept.Food Science and Nutrition Dept.
Dr. Majeed Al-Ani, Dr. Majeed Al-Ani, Food Science and Nutrition Dept.Food Science and Nutrition Dept.
They Disserve Our Effort!!B شكرًا