Autism

Autism - Etiology and associated disorders

Dr. Anil B. Jalan
M.D. , D.C.H. , M.C.P.S.
Paediatric Geneticist

Ms. Shefali Vaidya
M.A. ( Clinical Psychology )

Ms. Sudha Ojha
M.A. ( Clinical Psychology )

Introduction :- In 1943 Kanner reported a group of patients with varyingly severe developmental impairments of social skills, verbal and non-verbal communication skills. Males outnumber females in the ratio 4 : 1 . The disorder is manifested in the first year of life in about 31 % between age 1 and 2 in 44 % and between 2 and 3.5 years in 25 % ( Wilham and Marian, 1984 ). Incidence of seizures varies with age 20 % of patients with infantile autism have seizures which appears only in childhood or in adolescence. Approximately, 30 % of children do not show seizures in infancy or early childhood, will develop seizures in adolsence or as young adults . There is evidence for an organic basis for autism. Clancy et. al., ( 1969 ), listed 14, behavioural symptoms which indicate autism. If seven or more than seven of these symptoms are present, then the child should be considered for autism.

1. Not using correct posture while standing, less communicable with other people, treats other people as objects.
2. There is a lot of difficulty showing mixing and playing with other children.
3. They are hesitant to learn any new behavious or skills.
4. They resist changes in routine work.
5. They act as if they are deaf.
6. There is no eye contact established.
7. They like repetition and odd type of play.
8. They do not like anyone to cuddle them like a baby.
9. They are unusually attached to particular objects.
10. They are physically overactive.
11. They like to spin objects which are round.
12. They indicate needs of gesture.
13. They do not fear about realistic danger.
14. They laugh and giggle for no apparent reason.
15. Onset before 30 months of age.

Early infantile autsim is characterised by failure of the child to relate to its parents and other people, extreme withdrawal , inability to concentrate on anybody or anything. The child cannot emotionally respond nor tolerate emotional demands. They are noticed by the physician due to delay speech. If speech is present, there is nonsence rhyming echolalia and other idiosyncratic language may be present as an infant the autistic children do not show cuddly behaviours, social smile is either delayed or absent and the child does not antocipate postures prior to being picked up. The child likes to be alone in a constant environment, with its favourite toys. Than human beings. If the sameness is altered the child throws tantrums like, rage reactions. The eye contact in such patients are minimum or absent and they are indifferent to the attempts of others who try to engage them in play head banging, teeth grinding, whirling and rocking may lead to self - mutilation to such an extent, that the child’s life is in danger. They have a heightened awareness and sensitivity to some stimuli, for e.g. diminished responses to pain, and lack of startle response to loud noises. The child avoids situation which demands of him, so it is necessary for us to make use of his ritualistic mannerisms. His eccentric nature should be accepted. On close observation it is noticed that the autistic child tells us more by his action than he could ever consciously communicate in words. Some of the autsitic infant are hyperexcitable and irritable, they are relaxed only when held or rocked. The more retarded, the more autistic features some autistic chidren may show aggression, destructiveness including self - mutilation. At puberty, their evolving sexuality may produce new problems. Some older children have incontinence.

IQ in these patients is in the retarded range. It is difficult to assess the intellectual potential of the autistic child due to its deficit in language and socialization. Some children may perform well in non - verbal test whereas the ones with developed speech may have adequate intellectual capacity. Approximately, one - halt to two - third of all autistic children are severely retarded, who have an IQ below 50 % ( carr , 1976 ).

Theories about the cause of autism is doubtful. Autism in not induced by parents. The variety of agents are brain injury, constitutional culnerability, deficits in the reticular activating system, developmental aphasia. Recent evidence indicate that autism is neurophysiologic in origin. Autism occurs in histidinemia, tuberous sclerosis, toxoplasmosis, and cytomegalic inclusion disease, among other identifiable condtions. Some authorities suggest brain - stem localization, and the vestibular system, the lesion could be in strait at limbic system. Some say that autism is " primary deficit " ; in the processing of sensory information and others explain that autistic syndrome by a language deficit. There is a global neurologic dysfunction and thus a global lesion.

Many different therapies are used in patients with autism. The way to help these children is to develop a relationship with them and to communicate with them. The caretakers are the most important people to communicate with the autistic child. They are the onces who establish link with the child's fantancy world and the real world. A little patience, understanding and a good sense of humour are essential as far as the caretakers are means like engaging children to play with or in water, some of them enjoy the texture and the sand of sand trickling through their fingers ; they thus help us to involve with the child and play with the child. Rocking and swinging is what is liked by the autistic child and the communicator using this can breat through his inner world. Music elicits response from these children. Thus, it is necessary to creat a warm and pleasant climate for the child to interact with the communicator. His involvement in the real world activites is very slow, he can quickly with draw into his private world, but the aim of the caretaker is to extend his level of participation. In some cases there is acquisition of speech with behaviours and operant conditioning. Behaviours Therapy has also been used in controlling destructive, self - mutilating, and non - functional preservative behavious psychotherapy is of limited value. Tranquilizers are useful in controlling aggressive and self- mutilating out bursts Anti psychotic drugs are useful in impairing the stereotyping behaviour social withdrawal and ability to learn. Therapeutic residential setting may be helpful in those patients, who find it difficult to manage their children at home. Differential diagnosis of autism involves develop-mental aphasia, deafness and blindness. Autistic children show waxing and wanning of skills and behaviours.

EEG abnormalities occur in about 65 % of children with autism.

CT may show large ventricles or alternations in the proportions of left and right hemispheres some places the lesion more in the left temporal lobe or left hemisphere generally, some place in the right hemisphere and the normal asymmetry of the brain is not noticed in the CT scan serotonin level in whole blood is higher in autistic children while depamine - betahydroxylase levels is lower unusual levels of catecholamine metabolities in the urine is present. Zinc levels increase, whereas copper levels are the same as that of the normal children.

The prognosis for autistic children is guarded, and it primarily depends on the child's basic intelligence ( Knobloch, 1975 ). Educational placement is important than psycho - therapy for the good of the autistic child. However, psychological educational and hearing testing are an intergral part of the evaluation system. Those with speech and live a self - sufficient albeit isolated life in the community, but for most of the cases placement in the institution is the only choice. There relationship between autism and schizaphrenia is doubtful , cases where autistic children have developed schizophreniza are rare.

The DSM - IV classifies several ASDs :

1. Asperger's syndrome,
2. Pervasive developmental disorder ( PDD ) ( autistic disorder ),
3. Childhood disintigrative disorder
4. Rett Syndrome
5. Pervasive developmental disorders not otherwise specified ( NOS )( including atypical autism ) .

The defining , characteristic, and variable features of what are referred to in this article as the autistic spectrum disorders are shown in table no. 1. The DSM - I V criteria for the diagnosis of PDD - autistic disorder are shown in Box - 1. The Child Neurology Society Nosology Task Force heuristically distinguishes the autistic spectrum disorders from the developmental language disorders and NAMD on the basis of IQ, language, and sociability status.

1. Biotinidase deficiency - 20 % ( 1 / 5 )
2. Cytomegalo Virus Infection ( TORCH ) - 40 % ( 2 / 5 )
3. Severe Fatty Acid Oxidation Defect - 20 % ( 1 / 5 )
4. Moderate Fatty Acid Oxidation defect - 20 % ( 1 / 5 )

Subtypes :- A number of subtypes within the more general ASDs have been proposed in order to reduce heterogeneity in this population, to assist in the search for the etiology or etiologies eventuating in autistic behaviours, and to clarify prognosis on a more individual basis.

Subtypes 1 . Patients with Asperger's syndrome ( Asperger's 1944 ), in contrast to the more typical autistic child, tend to be high functioning ( Wing , 1981 ) and do not exhibit significant delays in language acquistion ( box no. 2 ). Hence concern as to the child's social interactions, communication skills, and behavior may not become apparent until after the age 3 years ( the upper limit age of presentation for the DSM - IV criteria for PDD to be met ). The general criteria elaborated in DSM - IV to define this disorder include :-

(1) severe and sustained impairment in social interactions ; and
(2) development of restricted, repetitive patterns of behavior, interests, and activities.

Tsai and colleagues ( Ghaziuddin et al, 1992 ) compared the various diagnostic criteria for Asperger's syndrome and suggest that the ICD - 10 ( as opposed to DSM-IV ) criteria of normal intellect plus social impairment, usually associated with clumsiness and all - absorbing interests, are the most likely to lead to accurate subtyping within the PDD spectrum on account of its homogeneity .

However, in a separate assessment of clumsiness as a diagnostic feature of Asperger's syndrome, these same investigators comment on the lack of a standardized definition of this term ( Ghaziuddin et al , 1992 ). In addition, recent reports suggest a relatively high frequency of patients in whom Tourette's syndrome ( TS ) and Asperger's syndrome coexist ( Berthier et al, 1993 ) ; Marriage et al, 1993 ; Nass and Gutman, 1995 ). The clinical distinction between tics, climsiness, and stereotypies is often blurred. Obviously, such clinical issues carry inferences about etiology, clinical course, and treatment , which need further refinement.

Subtype 2 . The DSM-IV also includes the diagnosis childhood disintegrative disorder, defined as

1 ) Normal development until at least age 2 years* followed by significant loss by age 10 years of acquired skills in at least two of the following five areas :
1. expressive of receptive language,
2. social or adaptive behaviour,
3. bowel or bladder control,
4. plays, or
5. motor skills ;

2 ) abnormalities in two of the following three areas :
a. social interactions
b. communication
c. range of behaviour, interests, and activities.

Although an epileptic aspect is not required ( EEG abnormalities or epilepsy ), this syndrome has qualities suggestive of an autistic variant of LKS footnote. For example, Deonna and colleagues ( 1993 ) reported two patients with tuberous sclerosis who had evidence of autistic regression after previously normal development in association with limbic pathology and epilepsy. Perez and colleagues ( 1993 ) reported four children with continuous spike wave during sleep who developed both autistic like and frontal type neuro-psychological symptoms. These authors suggest that “ autistic regression’’ is a potentially reversible syndrome reflecting epileptic dysfunction of the frontal lobes.


Such reports highlight the need for an EEG evaluation in the ASDs as well as in the DLDs.

Table no. 1. Autistic Spectrum Disorders

Discriminating features
1. Social deficit
2. Language disability
3. Need for sameness

Consistent features
1. Play impairment
2. Stereotyped behavious

Variable feature
1. Mental ability.

Table no. 2. Diagnostic Criteria for Autistic Disorder

A. Impairment in social interactions

 impairment use of nonverbal behaviours
 failure to develop peer relationship
 lack of sharing enjoyment , interest , achievement.
 lack of social / emotional reciprocity.

B. Impairment in communication

 delayed language development
 inability to initiate or sustain conversation
 echolalia / jargon
 impaired imaginative play

C. Restricted activities and interests

 excessive pre-occupation with interests
 inflexible routines or rituals
 stereotyped motor mannerisms
 preoccupation with parts of objects


From American Psychiatric Association : Diagnostic and statistical manual of mental disorders, ed 4 ( DSM-IV ), Washington , D.C., 1994 , American Psychiatric Press.

Table no. 3. Asperger’s Syndrome


A. Qualitative impairment in social interaction, manifested by at least two of the follwoing :
 impairment in use of nonverbal behaviors to regulate social interaction.
 failure to develop peer relationships.
 lack of spontaneous seeking to share enjoyments and interests.
 lack of social or emotional reciprocity.

B. Restricted repetitive and stereotyped behaviour, interests, and
activities, manifested by at least one of the follwoing :
 encompassion preoccupation.
 inflexible adherence to non-functional routines.
 stereotyped and repetitive motor mannerisms.
 persistent preoccupation with parts of objects.

C. Disturbance causes significant impairement in functioning.
D. No clinically significant language delay.
E. No clinically significant cognitive deficity
F. Criteria not met for another PDD diagnosis or schizophrenia


Table no. 4. Autistic Spectrum Disorders.


 Social deficits, rather than language deficits , may be key to defining the autistic spectrum disorders.

 If there is no language by age 5 to 6 yrs. language development is unlikely and the probable outcome is poor.

 Some children with autism may have subtle seizures and may benefit from anticonvulsants. If in any doubt , obtain an E.E.G.

 Fragile X syndrome is one of the most common known causes of autism. Obtain chromosomes to make a prenatal diagnosis on future siblings.


 Look for signs of parkinsonism in autistic children as a reflection of dopaminergic dysfunction.

 The child with autism mistakenly thought to have ADHD may become worse on stimulants.

 Early diagnosis is possible and important . Early and intensive intervention may make a significant difference.

 Although intellectual level is not a defining characteristic of the ASDs, it is an important predictor of long term outcome .



 Look carefully at peer relations and language prosody and pragmatics in the child with attentional and overfoucs issues, he may actually have Asperger’s disorder and not ADHD.

 Tuberous sclerosis is a common cause of autism . A careful examination of the skin is mandatory in all children with ASDs.

Discussion :- Medical disorders associated with Autism

A. Prenatal

1. First and second trimester bleeding
2. Subotimality ( ? )
3. TORCH infection
4. Thalidomide embryopathy

B. Perinatal

1. Hyperbilirubinemia
2. Hypoglycemia
3. Respiratory distress
C. Congenital

1. Cornelia de lang syndrome
2. Dandy Walker Syndrome
3. Goldenhar’s syndrome
4. Hydrocephalus
5. Hypo-melanosis of Ito
6. Microcephaly
7. Mobius’ syndrome
8. Oculo-cutaneous albinism
9. Tuberous sclerosis
10. Neurofibromatosis
11. Duchenne Muscular dystrophy

D. Metabolic Disorders

1. Adenylosuccinate Lyase deficiency
2. Addison’s disease
3. Adreno Leukodystrophy
4. Celiac Disease
5. Histidinemia
6. Hurler’s syndrome
7. Hyperthyroidism
8. Hyper-uricosuria
9. Lead encepahlopathy
10. Lipidosis
11. Phenyl-ketonuria
12. Hypo-thyroidism
13. Lactic Acidosis
14. Biotinidase deficiency


E. Chromosomal abnormalities

1. Trisomy 21
2. 18 q- , XYY , XXX
3. Fragile X syndrome
4. Marker chromosome syndrome
5. Sex Chromosome abnormalities

F. Epilepsy

1. Infantile spasms
2. Landau - Kelffner variant

G. Vascular

H. Infections

1. Meningitis
2. Herpes encephalitis

I. Trauma

Treatment :- Behavioural response and the lack thereof to pharmacologic manipulation of Dopaminergic and Setotonergic neurotransmitter systems have been used as arguments as to the possible neurochemical basis of Autism ( Mc Dougle et.al. 1994 ).

Table Educational interventions for young children with autism

1. Requirements

i ] Intensive behavioural intervention
ii ] Intensive language / communication intervention, including presenting
language visually as well as orally if comperehension of speech
is serverely compromised
iii ] Teaching parents appropriate behaviour management techniques

2. Potential educational settings ( the choice depends on the child’s
changing needs, close communication with the parents is mandatory )

i ] Daily intensive one - on - one systematic behavioural conditioning approaches by an adult trainer ( at home or in school. Need for temporary residential setting for intensive intervention exceptional in this age group )
ii ] Daily attendance in a specialized highly structured pre - school for
children with autism with a very high educator / pupil ratio
iii ] Daily attendance in a preschool for handicapped childrne with specialized
educators and an individual aide trained in management of children with
autism
iv ] Daily attendance in a specialized preschool with a mix of normal and handi-
caped children
v ] Daily attendacne in a regular, well structued preschool with an individual aide trained in management of children with autism
vi ] Daily attendance in a regular, well - structued pre - school with an experienced firm teacher, with / without provision of part - time individual help outside the classroom


Table Pharmacological intervention

1. Anticonvulsants e.g. - Valproate , Carbamazepine
2. Coticosteroids e.g. - Predinisolone , A.C.T.H.
3. Serotonin uptake inhibitors e.g. - Floxetine , Sertraline
4. Stimulants e.g. - Methylphenidate , Amphitamine
5. Tricyclic Antidepressant e.g. - Clomipramine , Imipramine
6. Adrenergic Blockers e.g. - Propranolol , clonidine
7. Dopamine Blockers e.g. - Haloperiodol , Respiridone

8. Other newer modalities
a. Natural Vit. A
b. Sodium ascorbate
c. Pyridoxine with Magnesium
d. Dimethyl Glycine

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