Causes. Etiology and Biochemical Abnormalities of
Autism
CHAPTER I
Alan Schwartz, M.D.
Medical Director: Holistic
Resource Center
29020 Agoura Road, Suite A-B
Agoura Hills, CA 91301 (818) 597-0966
Supporting a lecture given on Sunday October 10, 2004 at Conference:
Maximizing Children’s Potential: Treating Autism, PDD and AD(H)D
CHAPTER I:
An Introduction to Autism and its Characteristics
with a Brief Discussion of Related Disorders
What Is Autism?
Are Autistic Children retarded?
Are there Different Kinds of Autism?
What are the Autism Spectrum Disorders (ASD)?
What is Asperger's Syndrome?
What Is Rett Syndrome?
What is Childhood Disintegrative Disorder?
What is Tourette's Syndrome?
What is AD(H)D?
What are the Characteristics of the Autistic
Child?
What Is Autism?
Autism is a complex developmental disability that typically appears
during the first three years of life. It manifests as a disorder that affects
the functioning of the brain and other bodily processes.
Autism and its associated behaviors and manifestations have been
estimated to occur in 2 to 6 per 1,000 births (Centers for Disease Control and
Prevention, 2003). The reported incidence of autism has increased dramatically
in the last 30 years, and not just in the U.S.
Autism is four times more prevalent in boys than girls and knows no
racial, ethnic, or social boundaries. Family income, lifestyle, and educational
levels do not affect the chance of autism's occurrence, however certain
environmental influences certainly do.
Are Autistic Children retarded?
No, but they may fit the criteria for retardation if they are not
treated appropriately or early enough in the course of the disease. Autistic
children, once “normalized,” are as smart as any other children,
and many seem be more intelligent than average.
Are there Different Kinds of Autism?
Yes. When autism was first described by Dr Leo Kanner of Johns Hopkins
Hospital in 1943 (he categorized the symptoms after observing 11 children with
this disorder) the incidence was estimated to be one in every ten thousand
births.
At that time the condition seemed to be evident shortly after birth.
This type of birth-onset autism we now label Classical Autism. The incidence of
Classical Autism has not changed since the illness was first described. It
still occurs in about one or two out of every 10,000 births.
However, the kind of autism that predominates today differs from Dr.
Kanner’s Classical (“Infantile Onset”) Autism in that the
symptoms of autism do not appear right after birth, but rather much later in
the child’s development-often between one and two years of age (sometimes
sooner, sometimes later).
This variety of autism is called Delayed-Onset or Regressive Autism and
appears to be epidemic. The incidence of regressive autism is frighteningly
high and increasing. Today varies between one out of every 85 births ( Scotland
) to one out of every 160-300 births (most of the U.S. ).
Children with regressive autism often develop normally for the first
year of life, and sometime after that age they appear to regress or else fail
to progress development-ally.
What are the Autism Spectrum Disorders
(ASD)?
Autism today is listed as a psychiatric/neurological disorder (although
it clearly is a lot more than that), and represents one of five conditions
listed under the general heading of Pervasive Developmental Disorders (PDDs).
These include Asperger’s Syndrome, Rett Syndrome, Childhood
Disintegrative Disorder and a catch-all category called Pervasive Developmental
Disorder, Not Otherwise Specified [PDD-NOS].
These, together with attentional deficit disorders with or without
hyperactivity, tic disorders (including Tourette Syndrome) and obsessive and
compulsive disorders (OCD) are often classified as disorders on the autism
spectrum, because they all overlap in both symptomatology, and in many cases,
in commonly seen laboratory abnormalities.
What is Asperger’s Syndrome?
At about the time that Dr. Kanner was describing the manifestations of
the condition that he called “Early Infantile Autism” a German
scientist named Hans Asperger was describing a milder form of this condition
which has ever since born his name. Asperger Syndrome-afflicted individuals
exhibit high functioning and intelligence, but their social abilities are
limited as is their spectrum of interests.
What Is Rett Syndrome?
Rett syndrome is a true progressive retardation disorder that occurs
almost exclusively in females, and, like Classical Autism, is relatively rare
(occurring in one out of every 10,000 to 15,000 births.) It is caused by an
identified genetic defect, which results in autistic symptoms appearing after
6- 18 months of age.
Children with this disorder often wring their hands and exhibit severe
mental and developmental deficiencies. They withdraw socially, appear to not
recognize their parents or others and exhibit severe coordination and
communications impairments. Physical, occupational and speech therapies may be
of limited help in improving their functioning.
What is Childhood Disintegrative Disorder?
Very few children who have an autism spectrum disorder (ASD) diagnosis
meet the criteria for childhood disintegrative disorder (CDD). An estimate
based on four surveys of ASD found fewer than two children per 100,000 with ASD
could be classified as having CDD. This suggests that CDD is a very rare form
of ASD. It has a strong male preponderance.
Symptoms may appear by age 2, but the average age of onset is between 3
and 4 years. Until this time, the child has age-appropriate skills in
communication and social relationships. The long period of normal development
before regression helps differentiate this from delayed onset or regressive
autism.
What is Tourette’s Syndrome?
“Over 100 years ago, the French physician Georges Gilles de la
Tourette wrote an article in which he described nine individuals who, since
childhood, had suffered from involuntary movements and sounds and compulsive
rituals or behaviors. In his honor, this constellation of symptoms was named
Gilles de la Tourette's Syndrome.
Today, we recognize that Tourette's is a spectrum disorder, with some
people having a few tics and others having tics plus features of other
conditions such as obsessions, compulsions, inattention, impulsivity and mood
variability.” [tourettesyndrome.net]
What is AD(H)D?
The acronym AD(H)D stands for attentional deficit disorder (with or
without associated hyperactivity). Children with this disorder have trouble
paying attention, focusing, making good eye contact and remembering what has
been said to them. They are easily distracted. If also hyperactive they may be
fidgety, in constant motion, moody, quick to anger or to cry and some may be
aggressive at times.
Many children with ADHD have a SNP (Single Nucleotide Polymorphism: a
variance in the gene that codes a protein) for an important brain enzyme called
methionine synthase (associated with the D4 receptor for dopamine). The
function of this enzyme is to add methyl groups to certain fatty chemicals
called phospholipids that reside in the cell membrane. The term “methyl
group” refers to a carbon with three hydrogen atoms attached to it.
When the membrane-bound phospholipids acquire the methyl group they
influence the activity of certain channels in the cell membrane, which allow
calcium into the cell thereby activating it. The functional result of all this
is to make the brain alert and focused. Children with this variant gene do not
add methyl groups to the membrane-bound phospholipids as readily, and therefore
have trouble with attention and focus. We think that many autistic children
probably harbor the same dysfunctional enzyme.
As we shall see the methionine synthase gene is also important in one
other biochemical reaction of vital importance in the etiology of autism.
Like autism, ADD and ADHD occur more often in males, especially blond
males, and the incidence appears to be increasing. Many physicians and
scientists believe that the dramatic rise in ADHD diagnosed children, which
parallels that of autistic children, is a reflection of biochemical
dysfunctions that are commonly seen in autistic children as well.
What are the Characteristics of the Autistic
Child?
Autistic children generally exhibit the following characteristics:
- Problems in socialization: they often don’t interact
well or appropriately with others. Severely autistic children may almost
totally ignore others.
- Problems in communication: Autistic children may never
develop language, or may develop it only to lose it for a period of time, or
may develop language skills very slowly. Some exhibit echolalia: the tendency
to repeat words or phrases that they have just heard. Some can memorize whole
passages from movies they have seen or songs that they have heard, but not
understand what they are parroting. This defect appears to be due to a relative
deficiency in the production of Creatine, an energy molecule found throughout
the body and essential for speech and communication.
- Restricted patterns of behavior and interests: autistic
children are often limited in their interests and activities. They often are
very restricted in their imaginative play, often preferring to play with just
one toy or a part of a toy. For example, many autistic children enjoy watching
objects spin or move and become fascinated with the wheels on toy cars and
trucks.
- Repetitive behaviors (also called “stimming” or
self-stimulating behaviors) These include jumping up and down, making noises,
flapping the hands, moving the fingers in unusual and repetitive ways, head
banging, rocking and many others.
- Bizarre behaviors: some autistic children will regard an
object or person out of the corner of their eye rather than looking straight at
that person. Some will hold their fingers close to their eyes while moving
their fingers. Some will purpose-fully injure themselves by biting their own
body parts or by head banging. Toe walking is not uncommon.
- Signs of Intestinal Disturbances: Many autistic children will
press their abdomens against furniture or other objects in order to relieve
their intestinal discomfort. Many have bloated abdomens, diarrhea and
infrequent bowel movements, which are often foul-smelling. About 60% of
autistic children experience these signs of intestinal dysfunction. Many have
intestinal yeasts and bacteria that produce neurotoxic substances. About 20%
show hypertrophic (overgrown) lymph nodes in the intestinal tract (nodular
hyperplasia) and about 60% show evidence ! of inflammation and even ulcerations
throughout the GI tract.
- Obsessive and compulsive behaviors: like lining up toys and
other objects.
- Attentional deficits and hyperactivity: Autistic children are
often easily distracted, unable to focus or concentrate. They often don’t
make good eye contact. Many are very active. This problem, as in children with
just ADHD or ADD disorders, may be due to commonly seen dysfunctions in the
methionine synthase gene, previously alluded to. Remember that methionine
synthase in the cell membrane functions in the transfer of methyl groups to
membrane-bound phospholipids. When this methyl group transfer does not occur at
the appropriate rate then certain calcium channels (regulate by glutamate
receptors) don’t open sufficiently, and when calcium doesn’t enter
the neuron in sufficient amounts then the cell is insufficiently stimulated.
The end result is lack of attention and focus.
- Hypersensitivity to sensory stimuli. Many autistic children
are sensitive to loud sounds, crowd noise, bright lights and touch. Some like
to be swaddled tightly. Others have problems with the tastes and textures of
certain foods. Most are extremely picky eaters who crave carbohydrate-rich
foods and refuse to eat other, more nutritious foods. Sensory issues are often
related to dysfunctions in a class of proteins known as the metallothioneins
(me-TAL-oh-THIGH-oh-neens). Their function will be discussed in more detail
later in this narrative.
- Intestinal Dysfunction: many autistic children have problems
with digestion and assimilation of nutrients. They may have constipation or
diarrhea, smelly bowel movements, abdominal pains and bloating. Some show signs
of malnourishment, and some have retardation in their growth..
- Sleep Disturbances; many autistic children don’t sleep
well; many arise way too early in the morning.
- Tics: Tics are purposeless movements or sounds and are much
more common in autistic children. Perhaps one in five autistic children
experience tics.
- Restricted Dietary Desires: Autistic children are often
carbohydrate addicts and are frequently extremely picky in their food choices.
This makes it difficult to provide them with appropriate meals.
- Seizures: seizures are not found in most autistic children,
but they occur more frequently in autistic children than they do in the
non-autistic population.
- Coordination difficulties: These are not seen in all autistic
children but do occur in autistics more frequently than in non-autistic
children.
- Laboratory Abnormalities: There are certain characteristic
laboratory abnormalities that are frequently found in children with autism and
related disorders.
- Persistence of measles virus after the MMR vaccine. Dr.
Andrew Wakefield has presented some compelling data in this regard.
- Elevated serum copper to zinc ratios: These are seen in 85%
or more of autistic children (they average 1.63), according to data accumulated
at the Pfeiffer Clinic. The optimal ratio (as seen in non-autistic individuals)
is about 1.15.
- Elevated Free copper. Dr Walsh at the Pfeiffer Clinic has
found elevated free copper to be significantly higher in autistic children than
in controls. Free copper is an oxidizing agent and can damage organs and
tissues.
- Low levels of ceruloplasmin: Ceruloplasmin is a copper-binding
enzyme that protects the body from copper’s free-radical attack.
- Dysfunctional DPP IV: DPP IV (Dipetidyl Peptidase IV) is an
intestinal enzyme that helps break down small protein fractions from foods
called peptides. An inability to break down certain peptides from gluten,
casein and soy results in the elevation of certain potentially neurotoxic
peptides that form in the gut. (like casomorphin, gliadorphin, dermorphin,
etc). These in turn are absorbed and may adversely affect neurological and
immune function. The same enzyme (DPP IV) also appears on the surface of
certain immune cells and serves to signal the cell into activity. When this
enzyme is dysfunctional the immune system is compromised.
- Antibodies to myelin basic protein. These auto-antibodies are
seen in over 80% of autistic individuals. Antibodies to other brain proteins
have also been found.
- Other Harmful Antibodies: Many children with autism have
antibodies against VIP (vasoactive intestinal peptide), a small signaling
molecule produced by intestinal cells. VIP has many functions including
preventing autoimmunity, and autoimmune reactions as in the aforementioned
auto-antibodies to certain brain proteins, are common in autistic children.
- IgG food allergies; These are common in all of us and
autistic children in particular are often adversely affected by these allergies
which may manifest as behavioral abnormalities like ADD or ADHD, as intestinal
dysfunctions like irritable bowel, or in other ways.
- Metal Allergies
- Toxic Metal Overload: This is a controversial topic in
conventional medicine, but it really shouldn’t be. The evidence is
overwhelming that autistic children harbor much higher levels of toxic metals,
like mercury than do non-autistic children. Dr. Bradstreet found mercury levels
to be 8 times higher in autistic children than in non-autistic youth. Upwards
of 92% of autistic children show abnormally elevated levels of toxic metals.
- Gut dysbiosis: Dysbiosis refers to an imbalance in the type
and/or amount of gut organisms sufficient to cause harm. Intestinal bacteria,
protozoans and yeasts may promote intestinal irritation and leaky gut; they may
produce toxic substances and interfere with the proper digestion and
assimilation of nutrients from foods. Dysbiosis is usually diagnosed on a
comprehensive digestive stool analysis test (CDSA), and further clues to its
presence may be discerned on a microbial organic acid test (usually evaluated
on a sample of urine or blood).
- Metallothionein dysfunction: This will be discussed in the
next chapter.
- G-protein abnormalities: These will be discussed in the next
chapter
- Peroxisomal disorders:
- Under-methylation: This is seen in approximately 45% of
autistic children and, according to Dr William Walsh of the Pfeiffer Treatment
Center, is characterized by low levels of the neurotransmitters dopamine,
epinephrine and norepinephrine, elevated levels of histamine and a tendency to
have depression, oppositional defiant disorder and OCD (obsessive and
compulsive traits).
Methylation refers to the movement of a piece of a
molecule called the “methyl group,” which consists of a carbon atom
attached to three hydrogen atoms (abbreviated CP). Methylation reactions are
vital to our biological processes.
Under methylation is believed to be
due to mutations in at least two enzymes. One of these aberrant enzymes is
abbreviated MTHFR (Methylene TetraHydroFolate Reductase). This enzyme functions
to donate a methyl group to folic acid, a “B vitamin,” which then
becomes 5- methyl tetra hydro folate. The 5-methyl THF then passes the methyl
group to vitamin B12 (under the influence of methionine synthase), and by so
doing changes the B12 into its active form called methyl cobalamin. Methyl
cobalamin then immediately donates its newly acquired methyl group to
homocysteine, thereby converting homocysteine into methionine. Hence the methyl
group is passed around, like a football, from folic acid to vitamin B12 to
homocysteine
The end result and purpose of all this methyl transferring
(the process is called trans methylation) is the synthesis of methionine and
the elimination of homocysteine, a potentially dangerous amino acid.
The
synthesis of methylcobalamin, the active form of vitamin B12, also requires
adequate amounts of glutathione and SAM (S-adenosyl methionine-also made from
methionine). Some children with autism lack that part of the methionine
synthase molecule that binds to SAM. This causes problems in the synthesis of
methyl cobalamin. Children with autism often have high levels of mercury and
other substances which inhibit the production of glutathione and SAM. The
result is an additional diminishment in the production of methyl cobalamin.
It’s no wonder, therefore, that supplementing the missing methyl
cobalamin to autistic children is so often productive.
- Over-methylation: It isn’t clear what causes this
problem, which occurs in about 15% of autistic children and is characterized,
according to Dr. Walsh, by an overabundance of dopamine, epinephrine and
nor-epinephrine as well as low blood histamine. He is “absolutely certain
…that methionine and/or SAMe usually harm low-histamine (overmethylated
persons)..... but are wonderful for high-histamine (undermethylated) persons.
The reverse in true for [those with elevated histamine levels] (undermethylated
persons), who thrive on methionine, SAMe, Ca and Mg..... but get much worse if
they take folates & B-12! which can increase methyl trapping.”
Conditions that Dr Walsh feels are associated with over-methylation
include: anxiety/panic disorders, anxious-depression, hyperactivity, learning
disabilities, low motivation, "space cadet" syndrome, paranoid schizophrenia
and hallucinations.
- Genetic errors in hemoglobin synthesis that lead to “pyrrole
disorders.” These are seen in about 6-10% of autistic children and
may be diagnosed when elevated levels of kryptopyrroles appear in the urine.
This disorder is associated with an increased loss of vitamin B6 and zinc in
the urine. The loss of these nutrients disables many enzyme systems including
the metallothioneins. The good news is that by supplementing zinc and B6 this
problem can be overcome.
- Malabsorption: This is a common concomitant of MT
dysfunction, dysbiosis and impaired digestive function. It is seen in
approximately 85% of autistic children.
- Other enzyme errors have been found, including dysfunctions in
Catechol O-methyl transferase (COMT). This enzyme transfers a methyl group
to the catecholamine hormones: dopamine, epinephrine and norepinephrine. If
this function is unsuccessful than imbalances in these
neurotransmitter/hormones result.
Read Chapter II |
