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

mostafa@squ.edu.om / waly.mostafa@gmail.com