Definition , risk factors , diagnosis and treatment of infantile autism

1. Immunodefic
iency
diseases
associated
with purine
metabolism
By Rasha🩺and Asma 🩺
Biochemistry
🩺
Under
supervisio
n:
Dr.
Mohamme
d Mansour

2. Two different
immunodeficiency disorders
that are associated with
purine degradation:
PNP
(Purine nucleoside
phosphorylase)
deficiency
1
2
ADA
(Adenosine deaminase)
deficiency

3. Catabolism
of purines
c c
c c

4. I – PNP
deficiency
Autosoma
l recessive
disorder
*Increase
amounts of
dGTP.
*Only T
lymphocyte
are affected
*Recurrent
infection
*Neurodevelop
mental delay 🧠
1
2
3

5. II- ADA
deficiency
Autosoma
l recessive
disorder
1
2
Accumulati
on of
deoxyaden
osine
3 Build up of
ATP & dATP
4
Inhibition of
ribonucleotide
reductase
5 No DNA
synthesis

6. Immune
system
ARMY
OF
CELLS
DIFFERE
NT
TYPES
BLUEPRI
NT

7. Immune
system
GENE
MUTATI
ONS
SCI
D
SCID babies
typically die in
their 1st 2 years of
Bubb
le
baby
disea
se

8. Mutati
ons
Defecti
ve cells

9. ADA deficiency
dATP in turn inhibits ribonucleotide
reductase and prevents DNA synthesis, so
cells are unable to divide or synthesize
new DNA.
1 Accumulation of adenosine and 2-
deoxyadenosine.
2
2-deoxyadenosine behaves as cytotoxic
metabolite and generally considered the
primary cause of lymph toxicity in ADA-
SCID disease.
Build up of dATP and accumulation of
massive amounts of ATP in plasma,
erythrocytes and lymphoid tissue where it
impairs lymphocyte development and
function.
3
4

10. Symptom
s
Multiorgan pathology
1
2
3
4
5
Small or
underdeveloped
thymus
Lymphope
nia
Apoptosis
of
lymphocyte
s
Absence of
cellular and
humoral
immunity
Recurrent
infection (life
threatening)
1
2
3
4
5
6

11. Therapeutic
procedures
1
2
Fixing the HSC
mutation that produces
faulty immune cells.
Replacement of
mutated HSCs with
healthy ones.

12. Since 1990s
GENE
ADDITION
1 2
3
4
5
Before
transplantation,
patients are
given a low dose
of chemotherapy

13. The 1st SCID trial → over 20
years ago.
GENE
ADDITION
Last 30 babies developed → Good
working immune system
1
2
Therapeutic
procedures

14. 2
HSC
replaceme
nt
Removal of
defective
HSCs
Chemother
apy is toxic.
Usage of a
particular
Antibody
Transplanta
tion of
intact cells
From a
healthy
donor
Gene
addition
Fewer side
effects 😊🧠
Healthy
person 

15. By usingthese 2 complementary
approaches, correcting the mutated
gene of the patients own stemcells
and replacingtheir mutatedHSCs
with healthy ones, scientists and
physicians are helping the SCID
babiesbuildstrong functioning
immune systemand livelong
healthy lives.
CONCLUSI
ON

16. So far, both the gene therapy and
HSC replacement approaches
have shown a promising
preclinical and clinical data.
However, it is important to keep
in mind that theses results are
still early and the therapies must
be tested further.
We must keep the momentum
going with much work and effort
in human trials for better changes
CONCLUSI
ON

18. • What is infantile autism
• Causes of autism
• Autism Mechanism
• Symptoms
• Types
• Diagnosis
• Management

19. 🔴Autism Introduction
• Infantile autism or autistic disorder is a developmental disability characterized
by difficulties with social and language communication.
• It must be distinguished from several disorders including; repetitive behavior
,mental retardation experience worsening in the social skills and schizophrenia.
• Autism is associated with a combination of genetic and environmental factors.
• Autism affects information processing in the brain and how nerve cells and their
synapses connect and organize; how this occurs is not well understood.
• The Diagnostic of autism spectrum disorder (ASD).
• Early behavioral interventions or speech therapy can help children with autism
communication skills.
• Some autistic adults are unable to live independently.

20. • introduction
1000 people
Globally , the number of
affected people in autism
was estimated at 1–2 per
1,000 people worldwide. It
occurs 4-5 times more often
in males than females.

22. 🔴causes of autism /
Biochemical bases
There is a common cause at the genetic,
cognitive, and neural levels for autism's
Which has a strong genetic basis, although
these genetics are complex and
unknown
⚠Genetic Factors
1. rare mutations with major effectors
autism cannot be traced to single-gene
mutation or to a single chromosome
abnormality.
mutation that causes the autism is not present
in the parental genome, because autism links
with X chromosome.

23. Biochemical bases
🔴
2. rare multigene interactions of common genetic variants.
Many genes have been associated with autism through
sequencing the genomes of affected individuals and their
parents which do not change DNA sequencing but are
heritable and influence gene expression.

24. 🔴causes of autism /
Biochemical bases
⚠ inherited causes
The large number of autistic individuals with
unaffected family members may result from structural
variation—such as deletions, duplications or inversions
in genetic material during meiosis.

25. ⚠Environmental Factors
Risk factors during pregnancy may
be due to exposure to air
pollution, alcohol, smoking,
illicit drugs, toxins , cocaine,
insecticide, lead(Pb),
infectious diseases and
autoimmune diseases
MMR ( measles, mumps, rubella)
vaccine for causing autism.
Maternal nutrition &
inflammatory may damage
fetal tissues, exhibit genetic
problems or damaging the
nervous system.

26. 🔴 mechanism of autism
Autism's symptoms result from maturation-
related changes in various systems of the
brain.
How autism occurs is not well understood. Its
mechanism can be divided into two areas:
1. the pathophysiology of brain structures
and processes associated with autism,
Ex: synaptic activity dysfunction
2. the neuropsychological linkages between
brain structures and behaviors.
There is evidence that gut–brain axis
abnormalities lead to gastrointestinal
inflammation, autonomic nervous system
dysfunction, the immune system are a
pathway that may allow diseases originated in
the intestine to spread to the brain.

27. symptoms &
types of Autism Presented py :
TAISEER ALTAM

28. 🔴signs and symptoms of
autism
Parents often notice signs during the first
three years of their child's life.
These signs often develop gradually, as:
🔸Delay of language
🔸experience worsening in their
communication
🔸lack of social or emotional interaction
🔸sensory abnormalities are found in over
90% of those with autism, (for example,
distress from loud noises

29. SYMPTOMS
🔸 poor muscle tone, and toe
walking deficits in motor
coordination
Unusual eating behavior occurs .
🔸PREFER TO PLAY ALONE
These are linked to greater social
impairment, irritability, behavior
and sleep problems and mood
changes

30. 🔴signs and symptoms of autism
Other symptoms
0.5% to 10% of children with ASD
show unusual abilities, ranging
skills such as memorization of
unnecessary things having
extraordinarily rare talents made
from an autistic scientist
Showing superior skills in
perception and attention
in one direction , relative to the
general population.

31. 🔴types of autism
Until 2013 there were Four different types of autism spectrum include :
1. pervasivedevelopmental disorder-nototherwise specified (PDD-NOS),alsocalledatypical
autism
2.Asperger syndrome
3.Rett syndrome Ex:- difficultywithgrossandfinemotor skillsorrepetitive handflapping.
4.childhooddisintegrativedisorder(phenotype autism)
Ex:-avoidingeye contact.
Today there isjustoneAutismSpectrum Disorder(ASD): withtree levelsofseverity
.dividedintolow-,medium- orhigh-functioningautism basedonIQthresholds
Peoplewithhighfunctionalautismabletoliveindependentlyandperform necessarydailyactivities.

32. 🔴types of autism
PPD-NOS autism
• Because there is no easy
way to define the symptoms
of PPD-NOS , which ranged
from mild to very sever, the
diagnosis no longer exsist.
• The people with PPD-NOS
may be diagnosed at level
1,2 or 3 depending on the
severity of the sympoms

33. types of autism
🔴
Asperger syndrome
• Unlike PPD-NOS people with asperger
syndrome generally develop spoken language
in the same way as typically developing other
children but have a tough time with social
communication
• These difficulties become more obvious at they
get older and social expectation increase.
• People with this often very intelligent ,so some
times it called ‘’geek syndrome ‘’or ‘’litter
professor syndrome’’
• Asperger autistics are now considered to have
the level 1 autism spectrum.

34. types of autism
🔴
Rette syndrome
• Is a genetic disorder that
primarily affect girls and rare boys
.
• It is the only one of the former
autism spectrum disorders, that
can be diagnosed medically
• Symptomes of Rette include
social communication challenges
and loss of purposeful use of
one’s hand .

35. types of autism
• Broad autism phynotype or (childhood disinte grative
disorder)
Include the people of merest touch of autism
This sometimes described as having ‘’shadow syndrome’’
• Sbclinical syndromes include :
• Social awkwardness anxiety ;preference for same routine
& degree of discomfort for bright , loud noise.
• This type are common among family members of people
with full- blown autism
• Phynotye syndrome is helpful for autistic people to seek
with building social communication skills and coping with
sensory challenges .

37. 🔴Diagnosis
There is strong evidence that autism arises
very early intrauterine development, but it's
hardly diagnosed.
• Diagnosis is based on behavior,
characterized by deficits in social
communication and interaction across
multiple contexts, repetitive behavior, or
activities.
These deficits are present in early childhood,
typically before age three, and lead to
clinically significant functional impairment

38. • Autism may be underdiagnosed in women
and girls due to that it is primarily a male
genetic phenomena (karyotype ) X linkage
have the ability to raise the frequency and
severity of conditions in males, this is the
reason of why males are diagnosed 4-5
times more often than female
• Girls are often diagnosed later than boys

39. Diagnosis
Several diagnostic instruments are available:
1. the Autism Diagnostic Interview-Revised
(ADI-R) it is similar to parent interview to
evaluate cognitive, communication and family
skills
2.Autism Diagnostic Observation Schedule
(ADOS) uses observation and interaction rating
scale for child behavior. It used widely in
clinical environments to assess severity of
autism based on observation of children.
- Clinical genetics tests are often done after
autism symptoms already diagnosed which
would routinely assess the genome's copy
number variations.

40. 🔴management
The main goals when treating
children with autism are to:
1.decrease communication deficits .
2. increase quality of life and
functional independence.
🔸Families and the educational
system are the main resources for
treatment by behavior analysts,
special education teachers, speech
pathologists, and psychologists.
special education programs and
behavior therapy early in life can help
children acquire self-care,
communication, job skills and
decrease symptom severity

41. 🔴management
🔹Education
Educational interventions often
used include applied behavior
analysis, developmental models,
structured teaching, speech and
language therapy, social skills
therapy, and occupational therapy
and cognitive behavioral
interventions in adults without
intellectual disability to reduce
depression, anxiety, and obsessive-
compulsive disorder.

42. 🔴management
🔹Medication
Medications may be used to
prepare a child into home or
school when behavioral
treatment fails.
They may also be used for
health problems, such as
anxiety , stress autism
patient are given drugs or
anticonvulsants, with the
most common drug
antidepressants, stimulants,
and antipsychotics

43. 🔹Medication
1. antipsychotics as risperidone and aripiprazole are treating
aggressive and self-injurious behaviors.
2. antidepressants, such as fluoxetine and fluvoxamine, have
been shown to be effective in reducing repetitive
behaviors.
3. Stimulant medications as methylphenidate is beneficial for
some children with co-morbid inattentiveness or
hyperactivity.
No known medication relieves autism's core symptoms of
social and communication impairments.