From the Editors of

Early Warnings signs of Autism in Childern.

Hope and Help for Autism Families

Autism: Early Signs and Symptoms

What to look for and when to get help for your child
By Rita Shreffler, Executive Editor, Autism File utism rates have risen exponentially over the past two decades with nearly one percent of children in the U.S. now diagnosed with an autism spectrum disorder. With more and more families now dealing with an autism diagnosis than ever before, one thing has become clear: the earlier that treatments and therapies are implemented for children with autism, the more promising the outcomes. It therefore becomes key for parents to educate themselves on the early signs and symptoms associated with autism so that if there are concerns, appropriate treatment protocols can be put into place. There are three crucial areas of development in which the symptoms of autism typically manifest in young children: language, social interaction, and behavior, and there are widely divergent degrees of impairment within those categories. The popular saying, If youve seen one child with autism, youve seen one child with autism, carries a lot of meaning for professionals who work with children on the autism spectrum. One child may be quite skilled in certain areas and have only slightly impaired verbal skills, while another may have an utter lack of ability to communicate, yet both are on the autism spectrum. Parents, caregivers, and the medical community need to be alert for both the obvious red flags and the more subtle symptoms for a potential autism diagnosis to ensure that proper care is established at the earliest possible time. When do autism symptoms appear? Parents tend to describe the onset of autism symptoms in two general categories: 1. 2. Symptoms of autism are apparent from the time of birth Symptoms of autism appear following an extended period of good health and normal development, often 12 to 18 months of age

There are growing numbers of parents who report that their children fall into the second category of normal development followed by either regression, where the child loses previously acquired skills, or by a stall in making further developmental gains. When this phenomenon is observed, parents should be careful to review their childs health history and take note of any possible triggers, i.e. exposure to toxins, ensuring that any such triggers are removed to prevent worsening of symptoms in the coming months and years. Red flags for language development Developing speech and language appropriately are paramount for human interaction and impact nearly all areas of life. The inability to communicate effectivelyor at allwith others is a hallmark of an autism diagnosis. Parents and caregivers need to be alert for any of the following signs associated with lack of language skills. Report to a physician if your child: Repeats the same words or phrases over and over Talks in an abnormal tone of voice U ses an odd rhythm or pitch when speaking (e.g. sing-songy, robot-like or ends sentences as if asking a question) Refers to himself in the third person L iterally interprets all speech from others (doesnt pick up on humor or sarcasm, etc.) R esponds to a question by repeating it, rather than answering it. U ses language incorrectly: makes excessive grammatical errors or uses the wrong words altogether Has difficulty communicating wants or needs I s unable to understand simple statements or questions H as no speech at all or has lost previously acquired language abilities

Parents can identify signals of impaired language development in day-to-day activities, noting for example if a child doesnt point to pictures in books being read to him, or doesnt gesture for desired items such as food or a toy. Impaired Social Connectedness The manner in which people connect with others is intertwined with language development and the ability to communicate effectively. If speech and language are impaired, then it often follows that social interactions suffer as well. There are several signs parents need to recognize when considering social development in young children and relay to their childs physician so they can be addressed. Report to a health care provider if your child displays any of the following: Lack of eye contact Failure to respond when his or her name is called Resistance to holding and other forms of touch
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Obviously, if parents and professionals suspect something is amiss in a childs development from day one, protocols should be put in place immediately to address the noticed deficits. The second category is a little trickier: autism therapies may be delayed as caregivers try to decide if the child is just experiencing growing pains or perhaps has caught a cold or virus and will be back on track soon. A wait and see approach is not a viable option in getting the most from the many areas of intervention available today for children with autism.
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Apparent inability to hear at times A seeming preference for being alone vs. in the presence of others Resistance to play or interact with peers Unawareness of the feelings of others

Some of these signs are most apparent in situations where children encounter peers, such as play dates or outings in the park. It is often in these social situations that parents may notice for the first time that the manner in which a child interacts with others isnt quite the norm. Behavioral Concerns Behavioral difficulties encompass perhaps the most challenging area of concern on a day-to-day basis for parents of children with autism. Among the most pronounced and oftencited characteristics of autism is a strong preference for routine, and should this be disrupted, behavioral changes can become quite noticeable, often in the form of meltdowns. Talk to your physician about any of the following you observe in your child: P erforms repetitive movements such as spinning, hand-flapping or rocking D evelops specific rituals or routines and becomes disturbed if these are altered Seems to be constantly in motion I s fascinated by parts of an object such as spinning wheels on toy cars S hows sensory defensiveness to sound, light, and touch Seems oblivious to pain Engages in sustained unusual play Unusual posture or gait, including toe-walking N arrow restricted interests such as dates/calendars, weather, movie credits, numbers

concerns you have for your child. Write down everything your child eats each day along with activities and changes in your home such as getting new carpet or any other renovations, and any outings you make with your child such as trips to the grocery store or park. Also make note of any medicines or supplements your child has taken or any vaccines he has received. A growing number of parents and professionals now believe that autism is not an unavoidable genetic condition, but one that combines genetic predispositions triggered by environmental factors such as exposure to toxins and allergens. Recording all aspects of -- and changes to-- your childs environment will help in determining what medical underpinnings exist that may respond to biomedical treatment. Trust your instincts If you have concerns regarding any area of your childs development, schedule an appointment with a physician, ideally one who has clinical experience with ASD children. Be prepared to be persistent if your childs doctor minimizes your observations of impaired development or unusual behaviors. While many physicians are now looking more closely at early red flags for autism, not all are willing to proceed with anything other than a lets give it some time approach. The earlier interventions such as speech and occupational therapy, applied behavior analysis, and biomedical treatments are implemented, the better the long-term prognosis will be for your child.

Contact your childs doctor immediately for developmental evaluation if you observe any of the following in your son or daughter: Th e loss of any previous acquired language, social, or motor skills at any age B y six months or later: no big smiles or happy expressions B y nine months or later: lack of facial expressions or back and forth sharing of sounds B y 12 months: no babbling or back-and-forth gestures such as reaching, pointing or waving By 16 months: no words B y 24 months: no meaningful two-word phrases other than repeating or imitating what others have said

While children are all different whether autism is a factor or not, and may not match all behavioral descriptions in parenting books, if troubling or negative behaviors occur on a daily or near-daily basis, the wear and tear on the family can be significant. Its very important to address behavioral concerns early on to improve the childs long-term development and to reduce the stress upon the entire family. Keeping a diary Chances are that if youre reading this, you already have noticed some of the signs and symptoms typically associated with autism in your child. Keeping a diary to record your observations can be of huge assistance in determining the areas of greatest concern which will in turn impact any needed interventions. Tracking all external input can also help you figure out if there are environmental factors behind the developmental
THE AUTISM FILE Early Waring Signs of Autism in Children 3

Further Reading: The Autism Book: What Every Parent Needs to Know About Early Detection, Treatment, Recovery, and Prevention, by Robert Sears, MD, FAAP. (Little, Brown and Company, 2010.)

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What is autism?
And what can I do to help my child with autism?
By Nancy OHara, MD and Gail Szakacs, MD

All of our children live in a toxic world. Because of problems with glutathione metabolism (the methylation and sulfation biochemistry and their ability to detoxify), our children are much more sensitive to the toxins that each of us are exposed to on a daily basis. It is as if these children are our canaries. Where I grew up in West Virginia, they used to send canaries into the coal mines. If the canaries died, that meant the mine was too toxic for the miners. Because of their decreased ability or inability to detoxify, children with autism are our canaries. We need to help our children remove these germs, allergens, and toxins from their system in order to reach their full potential. Lets look at each of the medical problems that our children may be facing. There have been four major changes over the last few decades that I believe have led to the proliferation of autism. For our children, there is a genetic susceptibility, then repeated toxin exposures (as a fetus, exposures to maternal toxins, amalgams, fish consumption, and vaccinations; and as an infant and child, exposures to antibiotics, vaccinations, and toxins in our environment and foods). There is nutritional deterioration, a dependence upon nonorganic, processed, and refined foods. There is an increase in the number of vaccinations from 3 to > 34 during infancy and early childhood. Finally, and most importantly for our children, there is an increased susceptibility to all of these toxins because of a decrease in their ability to detoxify due to metabolic dysfunction, including increased oxidative stress and glutathione depletion as well as mitochondrial dysfunction. There are multiple clinical signs that indicate that these children have increased susceptibility in infancy and early childhood. So where do we begin? With each child, look at what he or she may need to get or get rid of to reach his or her fullest potential. He or she may need to get more nutrients, enzymes, or antioxidants like vitamins A, C, D, and E and glutathione. He or she may need to get rid of germs such as yeast or viruses, allergens such as gluten or phenolic foods, or metals such as lead or mercury. This can be a daunting process, but begin by building the foundation, and build one step at a time. Lets start with the gut. As Emerson has said, What lies behind us and what lies before us are small matters compared to what lies within us. He could have been referring to the gut. Whenever we begin a discussion about the treatment of autism, we need to start with the gut. Many of our children have problems with gut inflammation (a red, irritated, and inflamed gut lining), with dysbiosis (too many bad germs as compared to good germs) and abnormal permeability (because of the germs and the inflammation, molecules or allergens that are not supposed to be absorbed outside the gut are and cause allergies and sensitivities).

hat is autism? Is it a developmental disorder characterized by problems with social interactions, communication, and repetitive and restrictive behaviors? Yes, but that is a label, not a true understanding. Is it a brain disorder that is only genetically determined and untreatable? No, it is a genetically-influenced, environmentally-triggered disease of the brain and body that involves several vicious cycles and is treatable. Autism spectrum disorders affect approximately one in every 91 children in the United States and one in 57 boys. It is more common than Down syndrome, spina bifida, childhood cancer, and cystic fibrosis combined. One in 6 children now has a developmental or behavioral disorder. Each of our children is a tremendous gift. For our children in the autism spectrum, this gift is wrapped in many layers of wrapping paper. It is our job to begin to unwrap each layer to let the true gifts of our children shine through. These layers of wrapping paper, the vicious cycles, represent problems in the gut with digestion, absorption, nutritional defects and dysbiosis (more abnormal germs then good germs); problems in the immune system with allergies, inflammation, frequent infections, and autoimmune disorders; problems in the detoxification system with an inability to remove germs, allergens, chemicals, and metals from their systems, and resultant oxidative stress and mitochondrial dysfunction.

THE AUTISM FILE Early Waring Signs of Autism in Children 4

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What are some of the clues that my child may have gut problems? Difficulty breastfeeding Persistent colic Gastroesophageal reflux Food sensitivities Failure to thrive Wasted buttocks History of frequent antibiotics Abnormal posturing Hands in pants/probing/anal itching Self-injurious behavior Unexplained tantrums/crying Irritability (especially prior to bowel movements) Poor sleep Diarrhea Constipation Bloating Pain The next step in treating the gut is changing the childs diet. There is no such thing as junk food; it is either junk or food. Having a diet that is as free of processed foods, preservatives, added sugars, additives, and fillers is essential. Avoid excitotoxins (e.g., caffeine, MSG, and dyes), avoid phenolic foods if your child seems sensitive (e.g., grapes and strawberries), and avoid allergenic foods (kids crave that which they are sensitive to). Eat organically as much as possible (especially chicken, pears, apples, peppers, celery, strawberries, cherries, grapes, spinach, lettuce and potatoes). It may also be important to remove those foods that are hardest to digest, like milk, gluten, and complex carbohydrates (starches). If the gut is inflamed, has too many bad germs (dysbiosis), or does not have the right enzymes to process foods, then it will not absorb and digest foods appropriately. Think of a food like milk as a long paper clip chain. If the gut is working well, then the paper clip chain is broken down into two little paper clips (called amino acids) and this is absorbed, seen by the body as milk, and used as fuel appropriately for the brain. If the enzymes are not adequately present, the gut is inflamed, or there are too many dysbiotic germs, then the long paper clip chain is only broken down to a shorter chain. This chain (called a peptide) is seen by the body as an allergen, something foreign, is not used effectively by the body, and can mimic other opiate-like molecules leading to symptoms of brain fog, poor cognition, and abnormal behaviors like hyperactivity and rigidity. All of this happens because the body cannot effectively break down certain foods and use them as fuel. If the above measures, including removal of allergenic foods as well as casein (100% for at least 3 weeks) and
THE AUTISM FILE Early Waring Signs of Autism in Children 5
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As Dr. Michael Gershon points out in his book The Second Brain, everything that fuels and feeds our brain goes through our gut. When we talk about neurologic problems, such as autism, we must first start in the gut. So, what does cleaning up the gut mean? First, it means treating constipation. We cannot appropriately absorb and use nutrients or eliminate toxins unless we are having regular and daily bowel movements. Constipation is an obstacle to all further treatment options. So, first reestablish a rhythmic and repaired bowel pattern and then look at the underlying causes such as voluntary withholding, colon laxity or spasms, or abnormal flora (germs). Guide to treating constipation (in order of success): Fluids, prunes Fiber Magnesium citrate Vitamin C Senna Oils (olive, mineral, caster) Probiotics (beneficial germs) Antimicrobial/antifungal remedies Enemas/suppositories Prescription medications

gluten (100% for at least 3 months), does not help alleviate behavioral symptoms or heal the gut, then consider other healing diets such as GAPS (Gut and Psychology Syndrome by Dr. Natasha Campbell-McBride), BED (Body Ecology Diet by Donna Gates), or SCD (Specific Carbohydrate Diet by Elaine Gottschall). These diets, SCD for instance, are meant to stop the cycle of malabsorption and dysbiosis by removing the microbes food. Disaccharides (complex sugars) are harder to digest, not immediately absorbed and, therefore, left in the damaged gut to feed the bad germs (yeast, Clostridia, and parasites). SCD depends on only simple sugars in fruits, vegetables, and honey as well as meats and other proteins to heal the gut and eventually allow proper digestion. In addition to gut problems, our children may also have signs of immune system irregularities, such as a family history of autoimmune disease (thyroiditis, diabetes, inflammatory bowel disease); chronic ear, sinus, and throat infections; and food and environmental allergies and sensitivities. They may also have evidence of seasonal worsening of behavioral symptoms and/or cognitive improvement with fevers. These are all signs of immune dysregulation. Clues of immune dysregulation: Eczema Allergic shiners Allergic rhinitis Chronic mouth breathing Sleep apnea Asthma Warts Molluscum contagiosum Herpes Thrush/fungal skin infections

homocysteine back to methionine and is prone to damage by mercury and other heavy metals. As a result of this injury, methionine supplies run short. As a further consequence, there is a shortage of glutathione (the sticky sulfury molecule that is our bodys chief detoxifying molecule and a major antioxidant). A shortage of glutathione results in an unhappy milieu in the body, in more oxidative stress. This is where folinic acid, methyl B-12, and other methyl donors (such as betaine a/k/a TMG or trimethylglycine) are needed to treat underlying problems. Antioxidants such as vitamins A, C, D, E and especially glutathione are essential in decreasing the stress. When there is oxidative stress, there is increased susceptibility to toxins, chemicals, heavy metals, and pesticides, increased susceptibility to allergies and infections, and decreased production of glutathione and impaired efflux of toxins. What all this leads to is mitochondrial dysfunction. The mitochondria are the energy cells of our bodies and are central to all processes, neurologic and otherwise. Mitochondrial function is affected by heavy metals (mercury, arsenic, lead, cadmium, aluminum), pesticides, diesel exhaust, PCBs, germs and infection, poor nutrition, and oxidative stress/ low glutathione. Clues of mitochondrial dysfunction include: Low muscle tone weak suck, drooling, poor head control Constipation PICA Movement disorders posturing, writhing, jerking Hypotonia/hypertonia Seizures (acute, recurrent, hypoglycemic) Hypermobile/hyperflexible joints Decreased activity tolerance Curved back when sitting Difficulty knowing self in space Gross and fine motor delays Poor eye-hand coordination Speech (expressive and receptive) delays GI dysmotility, constipation, reflux Migraines Abnormal sweating Neurologic symptoms of mitochondrial dysfunction may be fixed or increased during stress (e.g., fasting, infections, exercise). Symptoms may be due to disturbed fat and carbohydrate metabolism (as with gut malabsorption and dysbiosis), hypoglycemia (the brain depends on a continual supply of sugar/glucose for fuel), and free radical production (as in oxidative stress). Although it was originally thought that only a small percentage of children with autism had mitochondrial
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If your child has evidence of immune dysregulation, the first step is still to heal the gut. Other options to consider may then be anti-inflammatories (a child whose tantrums subside with ibuprofen is a good candidate for further investigation and treatment of the immune system) and other immune modulators (e.g., TSO, gamma globulins, PPAR agonists, pycnogenol, curcumin, essential fatty acids, quercetin, and stinging nettles, to name a few). In addition to gut and immune problems, our children may also have metabolic problems. Metabolic problems are defects in the biochemical pathways of our body that cause stress. For example, as the research of Dr. S. Jill James has shown, we know that the chemistry of methylation (the process of taking food methionine and turning it into homocysteine and then ultimately to glutathione) is damaged in our children. One site of injury in this pathway is methionine synthase (MS) which recycles
THE AUTISM FILE Early Waring Signs of Autism in Children 6

dysfunction, recent studies indicate that the numbers may exceed 40-50% of our children. One study by Shoffner indicated that 78% of children with ASD had defects of oxidative phosphorylation, one type of mitochondrial dysfunction. Therefore, if, in addition to GI and immunologic dysfunction, you suspect mitochondrial dysfunction, the following labs and interventions should be considered: Labs Mitochondrial Isolated elevation of AST or ALT Lactate, pyruvate (serum, CSF) Ammonia Creatinine kinase Amino acids (elevated alanine:lysine ratio> 2.5) Organic acids (elevated fatty acids metabolites) Carnitine, free and total Skin biopsy (fibroblasts 50% inaccurate) Muscle biopsy (histiopath, EM, mtDNSA, OXPHOS)

clusters of other children and families that help you embark on your journey. Find a practitioner to discuss all of the signs, tests, and interventions for your child. Trust your gut and your childs! Good luck in your journey toward health and recovery in your child!

References

Gastrointestinal System
Ashwood P, Anthony A, Pellicer AA, Torrente F, Walker-Smith JA, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology; J Clin Immunol. 2003 Nov;23(6):504-17. DEufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996 Sep;85(9):1076-9. DSouza Y, Fombonne E, Ward BJ. No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder; Pediatrics. 2006 Oct;118(4):1664-75. Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders; J Pediatr. 2005 May;146(5):605-10. Pellicano R, Bonardi R, Smedile A, Saracco G, Ponzetto A, Lagget M, Morgando A, Balzola F, Bruno M, Marzano A, Ponti V, Debernardi Venon W, Ciancio A, Rizzetto M, Astegiano. Gastroenterology outpatient clinic of the Molinette Hospital (Turin, Italy) the 2003-2006 report, M. Minerva Med. 2007 Feb;98(1):19-23. Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease; J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S128-36.

Mitochondrial Interventions/Cocktail CoQ10 Carnitine Riboflavin Antioxidants (vitamins A, C, D, E, and GSH) B-6 and magnesium Other B vitamins (B-12, folinic acid, thiamin)

What can I do to help my child with autism? 1. 2. 3. 4. Heal the gut treat constipation, dysbiosis, inflammation Avoid what harms additives, toxins, allergens Give what heals nutrients, probiotics, essential fatty acids (EFAs) Fix metabolic and mitochondrial issues methyl B-12, folinic acid, B-6, magnesium, reduced glutathione (GSH), antioxidants, antiinflammatories.

Immune System
Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factoralpha in cerebrospinal fluid of autistic children.; Pediatr Neurol. 2007 Jun;36(6):361-5. Dietert RR, Dietert JM . Potential for early-life immune insult including developmental immunotoxicity in autism and autism spectrum disorders: focus on critical windows of immune vulnerability; J Toxicol Environ Health B Crit Rev. 2008 Oct;11(8):660-80. Dev Disord. Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics; J Autism. 1996 Aug;26(4):439-52. Ferrante P, Saresella M, Guerini FR, Marzorati M, Musetti MC, Cazzullo AG. Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children; Diabetes Technol Ther. 2003;5(1):67-73. Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, Barbato M, DEufemia P,

Autism is a label. Your child is not a label but a person suffering from medical problems that need to be discovered, addressed, and treated. Find these clues in your child, and find
THE AUTISM FILE Early Waring Signs of Autism in Children 7

Cardi E. Food Allergy and infantile Allergy; Panminerva Med. 1995 Sep;37(3):137-41.

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Pardo CA, Vargas DL, Zimmerman AW. Immunity, neuroglia and neuroinflammation in autism.; Int Rev Psychiatry. 2005 Dec;17(6):485-95. Singh VK, Lin SX, Newell E, Nelson C. Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism; J Biomed Sci. 2002 Jul-Aug;9(4):359-64. Vojdani A. Antibodies as predictors of complex autoimmune diseases; Int J Immunopathol Pharmacol. 2008 Apr-Jun;21(2):267-78. Warren, R.P., et al. Immune abnormalities in patients with autism; J Autism Dev Disord, 1986. 16(2): 189-97.

DIAgnosIs AutIsm: noW WhAt?

A sImplIfIeD BIomeDIcAl AppRoAch
By Dan Rossignol, MD, FAAFP

Metabolic & Mitochondrial Systems

Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in low-functioning autistic children: a pilot study; Biol Psychiatry. 1999 Aug 1;46(3):420-4. Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology. 2008 Jan;29(1):190-201. Gutsaeva DR, Suliman HB, Carraway MS, Demchenko IT, Piantadosi CA. Oxygen-induced mitochondrial biogenesis in the rat hippocampus.; Neuroscience. 2006;137(2):493-504. James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW. Metabolic ednophenotype and related genotypes are associated with oxidative stress in children with autism, Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56. MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res. 2007 Jan 10;176(1):149-69. Oliveira G, Diogo L, Grazina M, Garcia P, Atade A, Marques C, Miguel T, Borges L, Vicente AM, Oliveira CR. Mitochondrial dysfunction in autism spectrum disorders: a population-based study; Dev Med Child Neurol. 2005 Mar;47(3):185-9. R.H. Haas et al. The in-depth evaluation of suspected mitochondrial disease; Mol. Genet. Metab. (2008), doi:10.1016/j.ymgme.2007.11.018. Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley; Environ Health Perspect. 2007 Oct;115(10): 1482-9. Sokol DK, Chen D, Farlow MR, Dunn DW, Maloney B, Zimmer JA, Lahiri DK. High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression; J Child Neurol. 2006 Jun;21(6):444-9.

n 2002, my older son, Isaiah, was diagnosed with autism. At the time I had been practicing as a family physician for about five years. Prior to his diagnosis, Isaiah loved to get down on the floor and spin objects, and I thought it was cool, so I helped him. He also used to shake his hands back and forth in the air for hours. When I tried to shake my hands like him, I tired out in a couple of minutes. I couldnt figure out how he could do it for hours! He had a significant speech delay and walked very late. However, despite all of these problems, I did not have a CLUE that he had autism. I remember when my wife and I went to his psychological evaluation to determine what was wrong with him. He was evaluated by a pediatric neurologist and several psychologists, and we spent the morning with him during the testing. We were then told to go to lunch while the team met to determine a diagnosis. I remember as we sat in McDonalds eating French fries and cheeseburgers that my wife and I discussed that maybe the team would say he had autistic tendencies. It was quite a shock to us when Isaiah was actually diagnosed with autism! For the first year after his diagnosis, my wife started looking into biomedical treatments, which I considered quackery. I remember asking some pediatric neurologists about the gluten-free/casein-free (GF/CF) diet and being told that NO evidence existed in the medical literature as to whether or not this diet worked. When I finally realized that I needed to look into the medical literature for myself, I discovered some studies which reported that the GF/ CF diet appeared to be beneficial in some children with autism1,2. Shortly after this, my second son, Joshua, was also diagnosed with autism. I now realize that God allowed us to have two children with autism to give me a new career (taking care of children with autism) and to give us the ability to help other parents who also have children with autism. Now that I look back on things, I realize that we (me more so than my wife) wasted precious time because I didnt know what to do for my child. And I am a physician, and my wife is a nurse practitioner! Fortunately, there are currently many resources available to parents of a child with autism such as websites, books, and conferences. However, navigating through all of these possibilities can be daunting. The purpose of this article is to empower you, as a parent of a child with autism, by providing a starting point for biomedical treatments for your child.
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THE AUTISM FILE Early Waring Signs of Autism in Children 8

Initial laboratory testing: In many cases, a physician will need to order these tests for you. The Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP) check for anemia, platelet count (a high count is consistent with inflammation), and liver and kidney function. Thyroid. We find a significant number of children with autism who have hypothyroidism, which can mimic some of the symptoms of autism and impair development. A simple blood test called TSH can check for this problem. Iron deficiency can cause inattention and concentration problems12 . Low iron is also linked to lowered IQ13 . Iron supplementation in children with attention deficit hyperactivity disorder (ADHD) who have low iron levels has been shown to improve attention compared to a placebo 14 , and iron supplementation in children with autism has been shown to improve sleep15 . Ammonia and lactic acid are initial tests that can help determine if mitochondrial dysfunction exists, which can lead to low energy production and hypotonia (low muscle tone)11 and is potentially treatable with supplements like coenzyme Q10 and L-carnitine. Cholesterol. A cholesterol count less than 145 mg/dl in typical children has been shown to increase defiance and irritability and increase the chances of school suspension by three-fold16 . Supplementation with cholesterol in some children with autism may be beneficial 17. Cysteine is the precursor to glutathione and is the rate-limiting step for glutathione production. Low levels of cysteine reflect impaired glutathione production or increased glutathione utilization due to oxidative stress18 . Lead has been shown in some studies to contribute to autistic behaviors in some children19,20 . An elevated blood lead level reflects ongoing exposure and should prompt an investigation to find possible sources of lead in the house or environment. Magnesium has a calming effect, and lower levels have been found in children with ADHD21 and autism22 . Magnesium supplementation can decrease hyperactivity23 and improve certain autistic behaviors22 . Testosterone. A small percentage of children with autism have elevated testosterone24 , which can lead to aggression. The organic acid panel (OAT) is a specialized test that can measure markers of yeast, Clostridia, and other markers such as vitamin levels and mitochondrial function. Urinary porphyrin concentrations can reflect increased heavy metal or pesticide levels in the kidney and are markers of the metal burden in the body5 . Urinary neopterin is a marker of inflammation and tends to reflect autoimmunity in some children with autism25 . Elevated neopterin often predicts positive responses to anti-inflammatory treatments. Urinary oxidized DNA and RNA are markers of oxidative stress inside the cell26 , and children with elevated levels often have improvements with antioxidants. Urinary isoprostane is a marker of oxidative stress outside the cell26 . Again, antioxidants can be helpful when this is elevated. Stool testing can check for the presence of inflammation, dysbiosis (increased levels of yeast and abnormal bacteria), digestion, and absorption. Initially, the diagnosis of autism or other forms of autism, such as pervasive developmental disordernot otherwise specified (PDD-NOS, also called highfunctioning autism or mild autism), will generally come from a developmental pediatrician or a neurologist. Most neurologists will perform genetic testing (including chromosomal analysis and checking for fragile X syndrome), an MRI scan (to exclude some type of brain
THE AUTISM FILE Early Waring Signs of Autism in Children 9

structural problem), and an EEG (to look for seizure activity). An EEG is especially important because newer studies are reporting that about 60% or more of children with autism have subclinical seizure activity (subclinical means that you are not aware of this seizure activity) 3,4. We find significant improvements, especially in speech, in some children with autism when we treat seizures with medication.

After the initial diagnosis, there are specific laboratory tests that can be very helpful in either checking for other medical conditions (that could be exacerbating the autistic behavior) or defining underlying biomedical problems. Since autism is diagnosed based upon examination of the childs behavior, the actual diagnosis does not point to the underlying cause(s) of the disorder. We find that some of the core problems in autism include toxicity (including elevated levels of heavy metals, pesticides, and other chemicals)5,6, inflammation (potentially in the gastrointestinal tract and brain)7-9, oxidative stress (damage to tissue caused by free radicals, which are neutralized by antioxidants such as vitamins C and E)10, impaired glutathione production (which is the bodys main natural detoxifier and antioxidant)10, and impaired mitochondrial function (which are responsible for producing ATP, or energy)11. An in-depth discussion of each of these biomedical problems is beyond the scope of this article, but we will review simple laboratory tests and nutritional supplementation that any parent of a child with autism could start and which could potentially alleviate these problems and improve autistic behaviors. Initial treatments: There are certain treatments that parents can use to help improve certain behaviors in children with autism (and ADHD). The ideal treatment would be one that is wellwww.autismfile.com

been shown to improve sleep and gastrointestinal problems in children with autism when compared to a placebo38. Vitamin C: In a double-blind, placebo-controlled study, vitamin C (about 100 mg/kg) was shown to reduce stereotypical behavior (stimming) in individuals with autism compared to a placebo39. Methylcobalamin and folinic acid: Two studies have reported some improvements in certain autistic behaviors with the use of subcutaneous methylcobalamin injections (75 mcg/kg, requires a prescription) and oral supplementation of folinic acid (400 mcg twice a day)10-40. Methylcobalamin can also be given orally. Zinc: Deficiency has been correlated with inattention in children with ADHD41. Zinc deficiency has also been reported in autism42. In one study of 400 children, the use of zinc sulfate (150 mg/day that provided 40 mg/day of elemental zinc) was shown to improve ADHD symptoms compared to a placebo43. Magnesium and vitamin B-6: The use of these (given together) has been shown to improve autistic behaviors, including social interaction, communication, and stereotypical behaviors22, and improve hyperactivity in some children44. Typical doses are: magnesium at 6 mg/kg/ day and vitamin B-6 at 0.6 mg/kg/day22; sometimes higher doses are used under physician supervision. Pycnogenol: This has been shown to increase glutathione levels in children with ADHD45, decrease oxidative stress46, and improve attention, coordination, concentration, and hyperactivity compared to a placebo47. A typical dose is 1-2 mg/kg/day. Carnitine: Deficiency has been described in some children with autism48 and can impair mitochondrial function11. In one study of children with Rett syndrome, L-carnitine significantly improved sleep efficiency, energy level, and communication49. Carnitine has also been shown to improve attention and aggression in children with ADHD50 as well as lessen hyperactivity51. Generally, we use 50-100 mg/kg/day of L-carnitine or Acetyl-L-carnitine (preferring the latter as it penetrates into the brain better). Carnosine: This has strong antioxidant properties and also has been shown to decrease seizure activity. In one study, L-carnosine (400 mg twice a day) improved speech and social behavior compared to a placebo in children with autism52. Omega-3 fatty acids: Deficiency has been shown to increase hyperactivity, conduct problems, anxiety, and temper tantrums in typical children53. Infants not receiving omega-3 fatty acid supplementation in breast milk or infant
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studied, proven to be effective compared to a placebo, not too expensive, safe and tolerable, and can be done at home. Not many nutritional supplements fit into this category but several do. Many of these supplements are antioxidants that help to lower oxidative stress, which is a common finding in both ADHD27 and autism18. With the use of an evidence-based medicine approach, parents can get started with some simple biomedical treatments based upon the above laboratory testing and/or the childs behaviors. For example, if oxidative stress is elevated, then antioxidants can be added. If a child has an attention problem, then supplements or dietary changes could be made that have been shown to improve attention. Diet: Several studies have shown improvements in certain autistic behaviors, such as social isolation, communication, and overall behavior, with the use of a gluten-free/caseinfree diet1,2,28. Food additives, colorings, and preservatives can increase hyperactivity in typical children 29, so avoiding these products can be helpful. In children with autism, testing for food allergies and eliminating reactive foods has been shown to improve certain autistic behaviors 30. An organic diet can be helpful in eliminating pesticide exposures in children 31. A ketogenic diet can be helpful in some children with autism32. It should be noted that the use of specialized diets should be closely monitored by a physician or nutritionist. Sleep: If this is a problem, I usually start with trying to improve sleep because autistic behaviors are usually worsened with sleep deprivation33. One recent study revealed a defect in the ASMT gene that resulted in less melatonin production in some children with autism (this defect was also found in some of the parents)34. Several studies have shown improvement in sleep with the use of melatonin in autism35,36 and ADHD37. Melatonin at doses of 1-3 mg at bedtime is safe. Multivitamin: A general moderate-dose multivitamin has
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formula are about 2-4 times more likely to develop autism54. Several studies have demonstrated improvements with the use of omega-3 fatty acids in children with developmental coordination disorder55, ADHD56, and autism57,58. Omega-3 fatty acids can also have anti-seizure effects [59]. I usually recommend about 800 mg of EPA and 800 mg of DHA (sometimes higher), which is the approximate dose used in a recent double-blind placebo-controlled study of children with autism showing improvements in hyperactivity and stereotypical behavior58. I also generally recommend starting antioxidants before omega-3 fatty acid supplementation. Even though these treatments are available without a prescription, it is best to be under a physicians supervision when using these supplements and implementing significant dietary changes. Furthermore, a physician may be required to obtain certain laboratory tests and methylcobalamin injections. However, the supplements listed in this article are generally well-tolerated and can be helpful in improving certain behaviors in children with autism and ADHD. I would recommend sitting down with your childs physician to discuss these potential treatment options. May God bless you and your child as you journey together towards improvements and, I pray, eventual healing. Table 1 Doses of antioxidants and other supplements (based on the studies reviewed): Vitamin C: 100 mg/kg/day Acetyl-L-carnitine: 50-100 mg/kg/day L-carnosine: 200-400 mg twice a day Pycnogenol: 1-2 mg/kg/day Methylcobalamin injections: 75 mcg/kg 2-3 times per week Folinic acid: 400 mcg twice a day Omega-3 fatty acids: approx. 800 mg/day EPA and approx. 800 mg/day DHA Zinc: 20-40 mg/day of elemental zinc Melatonin: 1-3 mg, 30 minutes before bedtime Magnesium: 6 mg/kg/day Vitamin B-6: 0.6 mg/kg/day

References 1 Whiteley, P., et al., A gluten-free diet as an intervention for autism and associated spectrum disorders: preliminary findings. Autism, 1999. 3(1): p. 45. 2 Knivsberg, A.M., et al., A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci, 2002. 5(4): p. 251-61. 3 Lewine, J.D., et al., Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders. Pediatrics, 1999. 104(3 Pt 1): p. 405-18. 4 Chez, M.G., et al., Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav, 2006. 8(1): p. 267-71. 5 Nataf, R., et al., Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. Toxicol Appl Pharmacol, 2006. 214(2): p. 99-108. 6 Geier, D.A., et al., Biomarkers of environmental toxicity and susceptibility in autism. J Neurol Sci, 2009. 280(1-2): p. 101-8. 7 Vargas, D.L., et al., Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol, 2005. 57(1): p. 67-81. 8 Li, X., et al., Elevated immune response in the brain of autistic patients. J Neuroimmunol, 2009. 9 Torrente, F., et al., Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry, 2002. 7(4): p. 375-82, 334. 10 James, S.J., et al., Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr, 2004. 80(6): p. 1611-7. 11 Rossignol, D.A. and J.J. Bradstreet, Evidence of mitochondrial dysfunction in autism and implications for treatment. American Journal of Biochemistry and Biotechnology, 2008. 4(2): p. 208-217. 12 Konofal, E., et al., Iron deficiency in children with attention-deficit/ hyperactivity disorder. Arch Pediatr Adolesc Med, 2004. 158(12): p. 1113-5. 13 Lozoff, B., et al., Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev, 2006. 64(5 Pt 2): p. S34-43; discussion S72-91. 14 Konofal, E., et al., Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol, 2008. 38(1): p. 20-6. 15 Dosman, C.F., et al., Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol, 2007. 36(3): p. 152-8. 16 Zhang, J., et al., Association of serum cholesterol and history of school suspension among school-age children and adolescents in the United States. Am J Epidemiol, 2005. 161(7): p. 691-9. 17 Aneja, A. and E. Tierney, Autism: the role of cholesterol in treatment. Int Rev Psychiatry, 2008. 20(2): p. 165-70. 18 James, S.J., et al., Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet, 2006. 141(8): p. 947-56. 19 Lidsky, T.I. and J.S. Schneider, Autism and autistic symptoms associated with childhood lead poisoning. J Applied Research, 2005. 5(1): p. 80-87. 20 Accardo, P., et al., Autism and plumbism. A possible association. Clin Pediatr (Phila), 1988. 27(1): p. 41-4. 21 Kozielec, T. and B. Starobrat-Hermelin, Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnes Res, 1997. 10(2): p. 143-8. 22 Mousain-Bosc, M., et al., Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res, 2006. 19(1): p. 53-62. 23 Starobrat-Hermelin, B. and T. Kozielec, The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res, 1997. 10(2): p. 149-56. 24 Geier, D.A. and M.R. Geier, A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders. Neuro Endocrinol Lett, 2006. 27(6): p. 833-8. 25 Sweeten, T.L., D.J. Posey, and C.J. McDougle, High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry, 2003. 160(9): p. 1691-3. 26 Ming, X., et al., Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids, 2005. 73(5): p. 379-84. 27 Ross, B.M., et al., Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder. Nutr Neurosci, 2003. 6(5): p. 277-81.

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Millward, C., et al., Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev, 2008(2): p. CD003498. 29 McCann, D., et al., Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. The Lancet, 2007. 370(9598): p. 1560-7. 30 Lucarelli, S., et al., Food allergy and infantile autism. Panminerva Med, 1995. 37(3): p. 137-41. 31 Lu, C., et al., Organic diets significantly lower childrens dietary exposure to organophosphorus pesticides. Environ Health Perspect, 2006. 114(2): p. 260-3. 32 Evangeliou, A., et al., Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol, 2003. 18(2): p. 113-8. 33 Schreck, K.A., J.A. Mulick, and A.F. Smith, Sleep problems as possible predictors of intensified symptoms of autism. Res Dev Disabil, 2004. 25(1): p. 57-66. 34 Melke, J., et al., Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry, 2008. 13(1): p. 90-8. 35 Andersen, I.M., et al., Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol, 2008. 23(5): p. 482-5. 36 Garstang, J. and M. Wallis, Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev, 2006. 32(5): p. 585-9. 37 Van der Heijden, K.B., et al., Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psychiatry, 2007. 46(2): p. 233-41. 38 Adams, J.B. and C. Holloway, Pilot study of a moderate dose multivitamin/ mineral supplement for children with autistic spectrum disorder. J Altern Complement Med, 2004. 10(6): p. 1033-9. 39 Dolske, M.C., et al., A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry, 1993. 17(5): p. 765-74. 40 James, S.J., et al., Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr, 2009. 89: p. 1-6. 41 Arnold, L.E., et al., Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol, 2005. 15(4): p. 628-36. 42 Yorbik, O., et al., Zinc status in autistic children. J Trace Elem Exp Med, 2004. 17(2): p. 101-107. 43 Bilici, M., et al., Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry, 2004. 28(1): p. 181-90. 44 Mousain-Bosc, M., et al., Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. J Am Coll Nutr, 2004. 23(5): p. 545S-548S. 45 Dvorakova, M., et al., The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Rep, 2006. 11(4): p. 163-72. 46 Chovanova, Z., et al., Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder. Free Radic Res, 2006. 40(9): p. 1003-10. 47 Trebaticka, J., et al., Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry, 2006. 15(6): p. 329-35. 48 Filipek, P.A., et al., Relative carnitine deficiency in autism. J Autism Dev Disord, 2004. 34(6): p. 615-23. 49 Ellaway, C.J., et al., Medium-term open label trial of L-carnitine in Rett syndrome. Brain Dev, 2001. 23 Suppl 1: p. S85-9. 50 Van Oudheusden, L.J. and H.R. Scholte, Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids, 2002. 67(1): p. 33-8. 51 Torrioli, M.G., et al., A double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys. Am J Med Genet A, 2008. 146(7): p. 803-12. 52 Chez, M.G., et al., Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol, 2002. 17(11): p. 833-7. 53 Stevens, L.J., et al., Omega-3 fatty acids in boys with behavior, learning, and health problems. Physiol Behav, 1996. 59(4-5): p. 915-20. 54 Schultz, S.T., et al., Breastfeeding, infant formula supplementation, and Autistic Disorder: the results of a parent survey. Int Breastfeed J, 2006. 1: p. 16. 55 Richardson, A.J. and P. Montgomery, The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics, 2005. 115(5): p. 1360-6.

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56 Sinn, N., J. Bryan, and C. Wilson, Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial. Prostaglandins Leukot Essent Fatty Acids, 2008. 78(45): p. 311-26. 57 Meguid, N.A., et al., Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem, 2008. 58 Amminger, G.P., et al., Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry, 2007. 61(4): p. 551-3. 59 Schlanger, S., M. Shinitzky, and D. Yam, Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia, 2002. 43(1): p. 103-4.

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