Autism Spectrum Disorders: Making it All Make Sense

Kenneth A. Bock, MD, FAAFP, FACN

I have been asked to present the "wrap-up" lecture. I recognize that many of you may be floating in a sea of enormous amounts of information presented to you in the last three days, especially those of you here for the first time. These have been three days of power packed scientific and clinical information, infused with opportunity. Hopefully, this talk can relieve that sense of feeling overwhelmed, bring perspective to the situation, and allow a more relaxed swim amidst this sea of knowledge and information.

If I sound a little "folksy" here, please bear with me as I am going to depart from my usual fast paced information packed lectures, and take a different route. I plan to use select slides from various presentations in order to elucidate numerous points and highlights as take home messages. However, I have not included copies of slides because I want to retain the flexibility to adjust and adapt to the information and questions that have arisen during the presentations. I will frequently use the words of the presenters, as I attempt to bring order to the "chaos" that Dr. Usman so aptly refers to.

I can only imagine that listening to the biochemical genius of Dr. Pangborn must be daunting. Don't worry, you're joined by most of the physicians in this area as well. You don't need to worry about multiple gene defects and deletions or nucleosides/nucleotides synthesis disorders or exchange and depletion conditions. These are things that your physicians will need to be acquainted with, but are much less common in the regressive types of autism/encephalopathy that are the mainstay of this present epidemic. But there are important connections between the biochemical arena and the epidemiologic and clinical areas of knowledge. This includes Pangborn's reference to energy transfer deficiency and abnormalities in methylation and sulfation which are common in the majority of children with autism spectrum disorders, especially of the regressive subsets.

I believe that many affected children with autistic spectrum disorders have some type of mitochondrial dysfunction which although not at a level of a frank mitochondrial disorder, nevertheless represents more subtle dysfunction, affecting one or numerous processes in the complex system of energy production and/or transfer in the brain and other organs. Below the level of your conscious awareness, cellular processes are an ongoing life providing and supporting activity, which requires energy. In other words, it's not only overt visible activities such as running across a room, jumping on a rebounder, or picking up an object that requires energy. It's all those silent metabolic processes of cellular function, including ingress of nutrients and egress of wastes across cell membranes, cell receptor function, cell signaling processes, intracellular assembly, maintenance, and repair processes, and intra and intercellular transport and communication. When there is a problem with energy formation, energy transfer or energy utilization, it has profound ramifications on proper cell function. This is a key concept that I believe is applicable to many of our children.

You have heard so much about dysfunction in numerous organ systems in our children - including neurologic, immunologic, gastrointestinal and metabolic dysfunction. There is something that can provide an overarching explanation for this phenomenon of pervasive dysfunction. That is a toxic substance that we are all aware of; the mercury containing preservative, thimerosal. We've heard an excellent presentation describing the powerful adverse biochemical effects of mercury from Dr. Haley and the metabolic perturbations that it could cause. We've also heard about thimerosal's metabolic effects from Dr. Deth in relation to its inhibition of the methionine synthase enzyme, and from Dr. James in relation to the subsequent oxidant stress and resulting multi-cellular dysfunction. This is especially relevant in the context of certain genetic polymorphisms, which appear to be more prevalent in children with autism spectrum disorders. On a more macroscopic "and epidemiologic" level, the Geiers have provided evidence for the involvement of thimerosal in neurodevelopmental disorders, in sharp contrast to some of the recently published articles trying to refute this connection. All of this data serves to support the working hypothesis that genetically vulnerable children exposed to levels of mercury exceeding federal safety standards could develop neurodevelopmental/neurobiological disorders, with phenotypes including the entire range of the autism spectrum disorders (and I, as well as many of my DAN colleagues would extend this to the whole area of ADHD as well).

In fact, the epidemic of autism was reported and presented to you by many speakers, and I think it is fair to say that genetics do not cause epidemics, and therefore other explanations must be sought. An alternative explanation is that underlying genetic predispositions, acted on by overlying environmental factors or triggers, can certainly explain this epidemic. And this is the hypothesis that I, and many of my DAN colleagues, firmly believe explains the phenomenon of the autism epidemic that we have seen in the last two decades, and of which you have heard much supporting evidence over the past three days. A further extension of this genetic/environmental hypothesis would include Dr. Wakefield's research, which suggests that in genetically vulnerable children, mercury induced immunologic disturbances pave the way for aberrant reactions to the live combination MMR vaccination, resulting in either chronic atypical viral infections (such as measles), and/or autoimmune disorders.

Now, let's move to the brilliant work of Dr. Jill James concerning genomics, specifically genetic polymorphisms, and metabolics. Although her slides depicting metabolic pathways of methylation and transsulfuration are quite complex, the message is quite clear. Her concluding slide says it quite well and I quote, "The abnormal metabolic profile in children with autism is consistent with the abnormal genetic profile and strengthens the hypothesis that genetic susceptibility to oxidative stress and reduced methylation capacity may predispose these children to neurologic, immunologic, and gastrointestinal dysfunction that occurs with autism."

The treatment of these disorders (including increased oxidant stress and abnormal methylation and sulfation) includes some very basic nutrients; such as methylcobalamin (methyl B12), folinic acid, TMG and/or DMG, zinc, NAC, and glutathione). Preliminary studies have supported this and Dr. James, along with co-investigators including myself, Dr. Boris, Dr. Bradstreet, Dr. Usman and Dr. Cutler, are currently involved in a study looking at the genomics/metabolics of a larger number of children with autism spectrum disorders and the effects of zinc/TMG/Folinic acid/methylcobalamin/transdermal NAC on their clinical status as well as their metabolic profiles.

When it comes to treatment of children with autism spectrum disorders, there are some important generalized caveats that I would like to emphasize:

1. The treatment needs to be individualized. This is very important and is one reason why I would discourage you from jumping on every treatment that you read about or hear about. Dr. Baker referred to this whole process of individualization so well in his lecture when he was speaking of the diagnostic and treatment problem involved in patients with chronic illness of unknown cause. He refers to the process of thinking about each child as an individual, beginning with two simple questions:
   a. "Is there something for which this person has a special need, which if met would result in better function?" (such as nutrients)
   b. "Is there something of which this person should rid, which would result in better function?" (such as toxins and allergens) We spend a lot of time as clinicians figuring out what toxins are involved and how best to get rid of them, as well as which nutrients are best suited for each individual child.
2. Don't go it alone. Work with an experienced DAN practitioner who can help you navigate the journey through the myriad of evaluation and treatment possibilities that exists for this complex disorder.
3. Trust your intuition, as well as the doctor/health practitioner you choose to work with. The decisions frequently are not black or white, and clinical experience and knowledge as well as intuition and "the art of medicine" can be very important in terms of outcomes, dealing with potential transient adverse affects, as well as your comfort zone as a parent and partner in the treatment of your child.
4. Recognize that these children are metabolically "fragile" and that he or she may react adversely to an intervention that has significant positive effects in another child, or even in many other children. Also don't be discouraged by this. Report this to the doctor with whom you work, and hopefully this information can be used to chart additional navigational pathways.
5. Go slowly - add new interventions one at a time, allowing at least 3 to 4 days to a week between them to assess response/reaction. (Recognizing that sometimes it may take much longer for these responses/reactions to fully materialize). Don't go "Gang Busters" and add 10 things to your child's treatment at once - firstly because you increase the risk of adverse reactions, and secondly because you won't have any idea of which reactions pertain to which new intervention.
6. Let go of any guilt that you might feel regarding your role in your child's problems. This includes the fact that you may have brought him or her to the doctor when they received their thimerosal containing vaccines, and allowed them to, or even requested that they be administered. This was the standard of care at that time and you did nothing wrong.
7. A truly integrative approach includes the full spectrum biomedical approach, consisting of nutritional, immunologic, metabolic, gastrointestinal and toxicity/detoxification considerations. Additionally, in certain situations, adjunctive pharmacological management can be helpful as long as it is not a solo treatment, but is part of a comprehensive biomedical treatment program. An integrated treatment approach must also include the appropriate array of educational, behavioral, and therapeutic interventions. We can do our best to detoxify the cells, especially the neurons, and nourish them appropriately to support optimal function, but they need to be (re)taught and (re)trained via the numerous methodologies and programs that have been specifically developed to do just that.
8. Don't ever give up. Don't lose hope. The first diagnosis you may have received at the hands of a pediatric neurologist or developmental pediatrician no longer guarantees a grim prognosis. We are all involved in the recovery of more and more children, and although there is no guarantee, there is reason to be hopeful that your child can be a part of that sometimes miraculous, and always heartening, journey to recovery.