The Utilization of Laboratory Biomarkers to Predict and Prevent Neuroimmune Disorders Caused by Environmental Stressors
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BIOMEDICAL
The UTilizaTion of laboraTory biomarkers To PredicT and PrevenT neUroimmUne disorders caUsed by environmenTal sTressors
By Kendal Stewart, MD and Lisa Hunter Ryden, MT (ASCP), MBA
Kendal Stewart, MD, is the chief medical officer of the NeuroSensory Center of Austin. He is board certified in otolaryngology with fellowship training in neurotology/skull base surgery. His experience includes advanced training in neurosurgical, neurological and immunological disorders. Dr. Stewart has extensive experience with advanced neurological and audio-vestibular techniques and has authored two medically related patents in this area. He has had specific research interests in vestibular disorders, athletic injuries of the nervous system and processing/sensory integration disorders. Dr. Stewart has developed innovative and highly effective treatment protocols for neurological diseases including Meniere’s disease, imbalance, vertigo, autism spectrum disorders, and “postconcussion” syndrome. He has authored papers and is extensively involved in lectures and instructional courses for physicians, therapists and other health care professionals. Lisa Hunter Ryden, MBA, also has a degree in medical technology and post graduate coursework in microbiology, molecular genetics and immunology. She began her career as a clinical medical technologist and has spent the past 20 years in the medical diagnostics industry. She communicates her extensive knowledge of biomedical treatment to the autism community as a means to help physicians and parents develop a best practices model and develop a partnership to recover their children. Lisa hosts a program with Dr. Kendal Stewart on Autism One Radio, has given numerous public presentations on autism biomedical treatment, written several articles, and served as a parent advocate in political and legislative autism issues. Lisa and her husband have two boys. Their oldest son, Jake, suffered autistic regression at age 12 months, and was nonverbal until age 5. Today at age 8, he is recovering from his symptoms, speaking in sentences, writing, and learning to read.
A new case of autism is diagnosed every 20 minutes in the United States.
n 2007, the Centers for Disease Control and Prevention (CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network released data indicating that in many parts of the United States, about one in 150 children who are 8 years old had an autism spectrum disorder (ASD)1. The autism community, including educators and physicians who treat these children, believes that prevalence is much higher. While the cause for the autism epidemic remains the subject of much controversy, many parents report having babies who met every milestone until 12-18 months of age, after which they manifested regressive tendencies and
34 THE AUTISM FILE | www.autismfile.com | info@autismfile.com
I
loss of speech or eye contact, and acquired peculiar behaviors, seizures and/or gastrointestinal illness. These same parents report that these occurred following a round of childhood vaccines. Especially in the case of a first or only child, some parents do not realize that their child is not meeting the standard developmental milestones until the child is 3 years old or older. Parents may notice a speech delay and/or poor socialization followed by strange behaviors such as hand flapping, lack of eye contact, toe walking, and a desire for repetitive stimulation. The National Vaccine Advisory Committee 2 needs to fund independent
research toward the safety of vaccines so public trust in these vaccines can be restored and parents will have confidence that the current vaccine schedule is safe for all children of all genetic predispositions. The recent court cases of Poling and Banks have favored the plaintiffs as the rulings declared that vaccines contributed to both Hannah Poling’s and Bailey Banks’ autism. In the Poling case, Hannah was diagnosed with a mitochondrial disorder which allegedly caused her to have an adverse reaction to childhood vaccines3. Despite thousands of similar cases pending in the vaccine injury court, a single judge without a jury recently concluded the first of
ISSUE 33 2009
REPRINTED WITH PERMISSION © THE AUTISM FILE
three cases lacked sufficient evidence to prove that vaccines contributed to the respective child’s autism4. As a result of such recent court cases and conflicting information, many new parents have a hard time making educated decisions about how to safely vaccinate their children. In fact, pediatricians are reporting a growing public concern over vaccines, and many parents are asking about vaccine safety. To date, no adjustments have been made to the childhood vaccine schedule by the American Academy of Pediatrics or the CDC. As a safeguard, however, many parents have begun to request staggered or delayed vaccination schedules, much to the consternation of their pediatricians and contrary to the CDC warning that this is a dangerous practice that has not been proven to be effective or a safe community practice. Parents argue that they have not seen sufficient safety data to show that the current vaccine schedule has been proven to be safe with regard to all combinations and intervals of vaccines5. In fact, the majority of safety studies have been performed on one vaccine at a time, not multiple vaccine combinations. New vaccines are quickly added to the CDC childhood schedule, and more than 100 new vaccines are in clinical trial or in the development phase. Although there are specific genetic tests and protein biomarkers that can provide insight into the status of a child’s neuroimmune system, they are not used as an assessment tool for vaccine safety. Geneticists continue to look for a common gene or set of genes implicated in autism; however, they have found nothing conclusive after 10 years and millions of dollars spent in genetic research. While autism has grown to epidemic proportions, there is a general consensus among genetic researchers that there is no such thing
as a genetic epidemic. But it is widely accepted by these same researchers that there, most likely, is a genetic predisposition increasing the potential for specific children to undergo a regression in development following one or more vaccines, an environmental insult, or another oxidative stressor. Dr. Sandra Jill James, a research professor in the college of medicine department of pediatrics at the Arkansas Children’s Hospital, mapped the methylation pathway and demonstrated how impairments in this pathway can cause abnormal levels of specific amino acid biomarkers that directly reflect the potential for oxidative stress to impact children with a diagnosis of autism 6. Genetic polymorphisms in the methylation and transsulfuration pathways can lead to a significant decrease in glutathione production, thereby inhibiting the body’s ability to clear heavy metals and other fatsoluble toxins. In children with impaired pathways who are subsequently impacted by oxidative stressors, classic clinical presentations include reduced levels of methionine, cystathionine, cysteine, glutathione, methyl-B12, methyl-folate, and B6. Other notable biomarkers in children with autism include reduced levels of transferrin, cerumoplasmin, and L-carnitine, and increased levels of neopterin, biopterin, isoprostane, 8 OHG, ammonia, and lactic acid. Children with these findings typically present with many microbiological pathogens, including persistent viral, fungal, bacterial, and even parasitic infections due to poor modulation of the lymphocytic and, possibly, innate immune system. They can present with intestinal dysbiosis as indicated by an overgrowth of yeast and bacterial pathogens, which suppress the healthy balance of gut flora and impact the body’s inflammatory
status, nutrient absorption, and intestinal transition times. This abnormal state creates the “leaky gut” syndrome, which was first described by Dr. Andrew Wakefield7,8 and later was confirmed by multiple gastroenterologists. The consequence of leaky gut is that patients develop severe food intolerances and food sensitivities due to microscopic proteins leaking out of the gut and causing immunomodulation. Therefore, general clinical logic would link a group of genetic polymorphisms, which should produce specific identifiable protein or vitamin biomarkers, to abnormalities of immune function or modulation in these children that directly impact their ability to handle the oxidative stress of the normal vaccination schedule or chronic infectious state. At this time, no research studies have been performed on newborns to determine if there are associated abnormal biomarkers present at birth for children who eventually develop ASD. Therefore, as of this writing, no specific biomarker has been identified in infants who eventually develop ASD that could be used as a newborn screening tool, the usefulness of which would be
Geneticists continue to look for a common gene or set of genes implicated in autism; however, they have found nothing conclusive after 10 years and millions of dollars spent in genetic research. While autism has grown to epidemic proportions, there is a general consensus among genetic researchers that there is no such thing as a genetic epidemic. But it is widely accepted by these same researchers that there, most likely, is a genetic predisposition increasing the potential for specific children to undergo a regression in development following one or more vaccines, an environmental insult, or another oxidative stressor.
ISSUE 33 2009 REPRINTED WITH PERMISSION © THE AUTISM FILE info@autismfile.com | www.autismfile.com | THE AUTISM FILE 35
BIOMEDICAL
to assess the potential adverse effects of the oxidative stressors resulting from vaccination or exposure to other environmental toxins or chemicals. Physicians who specialize in ASD and other neurodevelopmental delays use biomarkers in older children to assess immune dysfunction, potential for toxic burden, presence of pathogens, and status of gastrointestinal function. Doing research with younger children who develop autistic tendencies can be quite difficult and is impacted by the referral pattern of pediatricians who typically are first consulted when a child begins showing early signs of abnormalities. These children are usually referred to a pediatric neurologist or psychiatrist for developmental or behavioral issues. Next, they may be referred to an allergist for their food allergies or to a gastroenterologist for gastrointestinal issues. The abnormal laboratory findings are typically only found once the child is seen by a physician specializing in autism, and this is usually later in the child’s development. Unfortunately, the American Medical Association and the American Academy of Pediatrics have not set up a best practices road map for treatment of ASD. Autism “centers of excellence” are emerging; but there are too few specialists available to treat the growing number of ASD patients. The National Newborn Screening and Genetics Resource Center (NNSGRC) is a cooperative agreement between the Maternal and Child Health Bureau’s genetic services branch and the University of Texas at San Antonio’s Health Science Center’s department of pediatrics. Its Web site provides a wealth of information about newborn screening, mainly in the United States, and lists the congenital disorders that can be detected in a newborn 9. While there is a set of national recommendations for which disorders are screened for in infants, each state determines its own panel, based
on cost to the state health department or other factors such as demographics. Newborn screening is performed within the first few hours of birth via a heelstick sample spotted on filter paper in the hospital. The dried blood samples are sent to the state health department and recorded for each newborn via a number system. Standard screening for genetic or protein abnormalities is then performed, and results are usually available to parents within two to four weeks. Abnormal results are communicated to physicians who refer parents to genetic counselors to advise them about the detected disorder. The filter papers for all newborn screenings are saved for a period of five to 10 years depending on the state requirement. There are very informative documents and transcripts of past meetings on the bioethics of newborn screening on the Web site for the President’s Council of Bioethics10. If we carefully examine the newborn screening profile performed today, we can find a long list of recognized congenital disorders of amino acid metabolism that potentially indicate
The holy grail for medical care on the issue of vaccination safety is identifying a consistent biomarker or group of biomarkers that could indicate a compromised immune status or a potentially poor response to oxidative stress.
36 THE AUTISM FILE | www.autismfile.com | info@autismfile.com
a poor response to oxidative stress. Many of the abnormalities in amino acid metabolism being screened for in the program represent the same markers that are recognized as abnormal in children who ultimately develop ASD. What we can’t determine, due to lack of scientific research, is if the abnormal levels of specific biomarkers found in children who currently have autism were present at the time of birth or in infancy. Based on current research at our institution and in other centers specializing in children with autism, we have reason to believe that the recognized amino acid concentration abnormalities in children with ASDs may have been present at birth and represent the genetic predisposition that defines the potential for autism development when environmental stressors are added to the equation. This will be the topic for a follow-up article. The state-mandated newborn screening program for metabolic core disorders has established reference ranges for only specific disease states; thus, reports are made only if the reference level is out of the defined range. For example, a disorder known as hypermethioninemia is only reported if the methionine levels are too high. It is widely known that many children with regressive autism present with hypomethioninemia (low levels of
ISSUE 33 2009
REPRINTED WITH PERMISSION © THE AUTISM FILE
Our hope is that autism will be redefined as a neuroimmune or epigenetic disorder with autistic regression as a symptom.
methionine). In addition, according to the Screening, Technology and Research in Genetics (STAR-G) project’s own literature, the amino acid disorder, hyperhomocysteinemia (too much homocysteine) is a disorder that can cause mental retardation and/or speech delays if left untreated. The recommended treatment is folic acid, B12, and B6 supplementation and a low methionine diet (no dairy or wheat)11 which is a recognized amino acid metabolic deficiency in some children with autism. In a study by Sarah Aldred, measured plasma amino acid levels in autistic patients, their siblings, and parents showed that children with ASD come from a family background of dysregulated amino acid metabolism, providing further evidence for an underlying biochemical basis for their condition12. In summary, it should be possible to retrospectively examine the amino acid concentrations of blood samples collected at birth in any state for abnormalities in amino acid biomarkers in children who were later diagnosed with regressive autism. The holy grail for medical care on the issue of vaccination safety is identifying a consistent biomarker or group of biomarkers that could indicate a compromised immune status or a potentially poor response to oxidative stress. Once recognized, a rapid, bedside test cartridge for these biomarkers could be developed for use prior to vaccinating the child. Additionally, a biomarker panel determination that a child could not safely be vaccinated according to the recommended vaccine schedule could reduce, if not eliminate, the need for parents to be questioned about medically-based vaccine exemptions. This biomarker panel would be valuable in states that do not allow religious or philosophical exemption from vaccines. We feel quite confident the identification of these biomarkers is close at hand. Pending the advancements in medical technology, parents are expected to vaccinate their children without question.
ISSUE 33 2009
References
1 CDC Web site, http://www.cdc.gov/ ncbddd/autism/overview.htm
The best advice that we can give them is to educate themselves before vaccinating their children and to consider the legal and ethical options available in their state. Newborn screening presents significant bioethical challenges. There is increased liability in the event of a false-positive or false-negative test, which can dramatically alter a course of treatment in congenital disorders. Most likely, many parents would not want their child to have a label of “autistic” at birth. In the age of personalized medicine, based on individual genomic differences, it will eventually be possible for every single individual to have a genetic profile performed at birth to assess genetic risk factors for certain diseases. For insurance reporting, the implications of genomic profiling are likely to cause many to fear discrimination by disease state, and this information is likely to be used to determine the cost of insurance coverage. We will probably need legislation to protect individuals from discrimination based on genomic profiling. We know certain individuals can smoke without developing lung cancer or emphysema, yet others, non-smokers even, develop smokingrelated diseases based on their genetic predisposition. There is growing research that we can change the way our genes are expressed with biomedical or dietary intervention, even if we cannot change our genes. In short, we should be discussing issues now. As there continues to be a surge in epigenetics (the codependent role of environment and genes) we will need to be proactive with the ethical issues surrounding our future generations. Our hope is that autism will be redefined as a neuroimmune or epigenetic disorder with autistic regression as a symptom. For parents of a child with autism, these ethical issues are of little concern when we discuss the possibility of recognizing risk factors at birth and preventing even one more case of autism … perhaps even staunching the epidemic.
NVAC Web site, http://www.hhs.gov/ nvpo/nvac/index.html
2
Generation Rescue Web site, http:// www.generationrescue.org/cases/ index.htm
3
Autism Omnibus Web site, http:// www.uscfc.uscourts.gov/omnibusautism-proceeding
4 5 Fourteen Studies Web site, http:// www.fourteenstudies.org/studies.html
James SJ et al., Metabolic biomarkers of increased oxidative stress and impaired methyllation capacity in children with autism. Am J Clin Nutr. 2004 Dec; 80(6):1611-7. http://www. ajcn.org/cgi/reprint/80/6/1611
6 7 Presentation on Autistic Enterocolitis, http://www.thoughtfulhouse. org/0405-conf-awakefield.htm
Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, Walker-Smith JA. Enterocolitis in children with developmental disorder. American Journal of Gastroenterology 2000;95:2285-2295
8 9 National Newborn Screening and Genetic Resource Center (NNSGRC) Web site: http://genes-r-us.uthscsa. edu/
The President’s Council on Bioethics Web site documents: http://www. bioethics.gov/reports/newborn_ screening/chapter3.html
10
http://www.bioethics.gov/reports/ newborn_screening/Newborn%20 Screening%20for%20the%20web.pdf The Screening, Technology and Research in Genetics (STAR-G) Project http://www.newbornscreening.info/ index.html
11 12 Aldred S. Plasma Amino Acid Levels in Children with Autism and Their Families, J Autism Dev Disord. 2003 Feb; 33(1): 93-7
REPRINTED WITH PERMISSION © THE AUTISM FILE
info@autismfile.com | www.autismfile.com | THE AUTISM FILE
37
BIOMEDICAL
The UTilizaTion of laboraTory biomarkers To PredicT and PrevenT neUroimmUne disorders caUsed by environmenTal sTressors
By Kendal Stewart, MD and Lisa Hunter Ryden, MT (ASCP), MBA
Kendal Stewart, MD, is the chief medical officer of the NeuroSensory Center of Austin. He is board certified in otolaryngology with fellowship training in neurotology/skull base surgery. His experience includes advanced training in neurosurgical, neurological and immunological disorders. Dr. Stewart has extensive experience with advanced neurological and audio-vestibular techniques and has authored two medically related patents in this area. He has had specific research interests in vestibular disorders, athletic injuries of the nervous system and processing/sensory integration disorders. Dr. Stewart has developed innovative and highly effective treatment protocols for neurological diseases including Meniere’s disease, imbalance, vertigo, autism spectrum disorders, and “postconcussion” syndrome. He has authored papers and is extensively involved in lectures and instructional courses for physicians, therapists and other health care professionals. Lisa Hunter Ryden, MBA, also has a degree in medical technology and post graduate coursework in microbiology, molecular genetics and immunology. She began her career as a clinical medical technologist and has spent the past 20 years in the medical diagnostics industry. She communicates her extensive knowledge of biomedical treatment to the autism community as a means to help physicians and parents develop a best practices model and develop a partnership to recover their children. Lisa hosts a program with Dr. Kendal Stewart on Autism One Radio, has given numerous public presentations on autism biomedical treatment, written several articles, and served as a parent advocate in political and legislative autism issues. Lisa and her husband have two boys. Their oldest son, Jake, suffered autistic regression at age 12 months, and was nonverbal until age 5. Today at age 8, he is recovering from his symptoms, speaking in sentences, writing, and learning to read.
A new case of autism is diagnosed every 20 minutes in the United States.
n 2007, the Centers for Disease Control and Prevention (CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network released data indicating that in many parts of the United States, about one in 150 children who are 8 years old had an autism spectrum disorder (ASD)1. The autism community, including educators and physicians who treat these children, believes that prevalence is much higher. While the cause for the autism epidemic remains the subject of much controversy, many parents report having babies who met every milestone until 12-18 months of age, after which they manifested regressive tendencies and
34 THE AUTISM FILE | www.autismfile.com | info@autismfile.com
I
loss of speech or eye contact, and acquired peculiar behaviors, seizures and/or gastrointestinal illness. These same parents report that these occurred following a round of childhood vaccines. Especially in the case of a first or only child, some parents do not realize that their child is not meeting the standard developmental milestones until the child is 3 years old or older. Parents may notice a speech delay and/or poor socialization followed by strange behaviors such as hand flapping, lack of eye contact, toe walking, and a desire for repetitive stimulation. The National Vaccine Advisory Committee 2 needs to fund independent
research toward the safety of vaccines so public trust in these vaccines can be restored and parents will have confidence that the current vaccine schedule is safe for all children of all genetic predispositions. The recent court cases of Poling and Banks have favored the plaintiffs as the rulings declared that vaccines contributed to both Hannah Poling’s and Bailey Banks’ autism. In the Poling case, Hannah was diagnosed with a mitochondrial disorder which allegedly caused her to have an adverse reaction to childhood vaccines3. Despite thousands of similar cases pending in the vaccine injury court, a single judge without a jury recently concluded the first of
ISSUE 33 2009
REPRINTED WITH PERMISSION © THE AUTISM FILE
three cases lacked sufficient evidence to prove that vaccines contributed to the respective child’s autism4. As a result of such recent court cases and conflicting information, many new parents have a hard time making educated decisions about how to safely vaccinate their children. In fact, pediatricians are reporting a growing public concern over vaccines, and many parents are asking about vaccine safety. To date, no adjustments have been made to the childhood vaccine schedule by the American Academy of Pediatrics or the CDC. As a safeguard, however, many parents have begun to request staggered or delayed vaccination schedules, much to the consternation of their pediatricians and contrary to the CDC warning that this is a dangerous practice that has not been proven to be effective or a safe community practice. Parents argue that they have not seen sufficient safety data to show that the current vaccine schedule has been proven to be safe with regard to all combinations and intervals of vaccines5. In fact, the majority of safety studies have been performed on one vaccine at a time, not multiple vaccine combinations. New vaccines are quickly added to the CDC childhood schedule, and more than 100 new vaccines are in clinical trial or in the development phase. Although there are specific genetic tests and protein biomarkers that can provide insight into the status of a child’s neuroimmune system, they are not used as an assessment tool for vaccine safety. Geneticists continue to look for a common gene or set of genes implicated in autism; however, they have found nothing conclusive after 10 years and millions of dollars spent in genetic research. While autism has grown to epidemic proportions, there is a general consensus among genetic researchers that there is no such thing
as a genetic epidemic. But it is widely accepted by these same researchers that there, most likely, is a genetic predisposition increasing the potential for specific children to undergo a regression in development following one or more vaccines, an environmental insult, or another oxidative stressor. Dr. Sandra Jill James, a research professor in the college of medicine department of pediatrics at the Arkansas Children’s Hospital, mapped the methylation pathway and demonstrated how impairments in this pathway can cause abnormal levels of specific amino acid biomarkers that directly reflect the potential for oxidative stress to impact children with a diagnosis of autism 6. Genetic polymorphisms in the methylation and transsulfuration pathways can lead to a significant decrease in glutathione production, thereby inhibiting the body’s ability to clear heavy metals and other fatsoluble toxins. In children with impaired pathways who are subsequently impacted by oxidative stressors, classic clinical presentations include reduced levels of methionine, cystathionine, cysteine, glutathione, methyl-B12, methyl-folate, and B6. Other notable biomarkers in children with autism include reduced levels of transferrin, cerumoplasmin, and L-carnitine, and increased levels of neopterin, biopterin, isoprostane, 8 OHG, ammonia, and lactic acid. Children with these findings typically present with many microbiological pathogens, including persistent viral, fungal, bacterial, and even parasitic infections due to poor modulation of the lymphocytic and, possibly, innate immune system. They can present with intestinal dysbiosis as indicated by an overgrowth of yeast and bacterial pathogens, which suppress the healthy balance of gut flora and impact the body’s inflammatory
status, nutrient absorption, and intestinal transition times. This abnormal state creates the “leaky gut” syndrome, which was first described by Dr. Andrew Wakefield7,8 and later was confirmed by multiple gastroenterologists. The consequence of leaky gut is that patients develop severe food intolerances and food sensitivities due to microscopic proteins leaking out of the gut and causing immunomodulation. Therefore, general clinical logic would link a group of genetic polymorphisms, which should produce specific identifiable protein or vitamin biomarkers, to abnormalities of immune function or modulation in these children that directly impact their ability to handle the oxidative stress of the normal vaccination schedule or chronic infectious state. At this time, no research studies have been performed on newborns to determine if there are associated abnormal biomarkers present at birth for children who eventually develop ASD. Therefore, as of this writing, no specific biomarker has been identified in infants who eventually develop ASD that could be used as a newborn screening tool, the usefulness of which would be
Geneticists continue to look for a common gene or set of genes implicated in autism; however, they have found nothing conclusive after 10 years and millions of dollars spent in genetic research. While autism has grown to epidemic proportions, there is a general consensus among genetic researchers that there is no such thing as a genetic epidemic. But it is widely accepted by these same researchers that there, most likely, is a genetic predisposition increasing the potential for specific children to undergo a regression in development following one or more vaccines, an environmental insult, or another oxidative stressor.
ISSUE 33 2009 REPRINTED WITH PERMISSION © THE AUTISM FILE info@autismfile.com | www.autismfile.com | THE AUTISM FILE 35
BIOMEDICAL
to assess the potential adverse effects of the oxidative stressors resulting from vaccination or exposure to other environmental toxins or chemicals. Physicians who specialize in ASD and other neurodevelopmental delays use biomarkers in older children to assess immune dysfunction, potential for toxic burden, presence of pathogens, and status of gastrointestinal function. Doing research with younger children who develop autistic tendencies can be quite difficult and is impacted by the referral pattern of pediatricians who typically are first consulted when a child begins showing early signs of abnormalities. These children are usually referred to a pediatric neurologist or psychiatrist for developmental or behavioral issues. Next, they may be referred to an allergist for their food allergies or to a gastroenterologist for gastrointestinal issues. The abnormal laboratory findings are typically only found once the child is seen by a physician specializing in autism, and this is usually later in the child’s development. Unfortunately, the American Medical Association and the American Academy of Pediatrics have not set up a best practices road map for treatment of ASD. Autism “centers of excellence” are emerging; but there are too few specialists available to treat the growing number of ASD patients. The National Newborn Screening and Genetics Resource Center (NNSGRC) is a cooperative agreement between the Maternal and Child Health Bureau’s genetic services branch and the University of Texas at San Antonio’s Health Science Center’s department of pediatrics. Its Web site provides a wealth of information about newborn screening, mainly in the United States, and lists the congenital disorders that can be detected in a newborn 9. While there is a set of national recommendations for which disorders are screened for in infants, each state determines its own panel, based
on cost to the state health department or other factors such as demographics. Newborn screening is performed within the first few hours of birth via a heelstick sample spotted on filter paper in the hospital. The dried blood samples are sent to the state health department and recorded for each newborn via a number system. Standard screening for genetic or protein abnormalities is then performed, and results are usually available to parents within two to four weeks. Abnormal results are communicated to physicians who refer parents to genetic counselors to advise them about the detected disorder. The filter papers for all newborn screenings are saved for a period of five to 10 years depending on the state requirement. There are very informative documents and transcripts of past meetings on the bioethics of newborn screening on the Web site for the President’s Council of Bioethics10. If we carefully examine the newborn screening profile performed today, we can find a long list of recognized congenital disorders of amino acid metabolism that potentially indicate
The holy grail for medical care on the issue of vaccination safety is identifying a consistent biomarker or group of biomarkers that could indicate a compromised immune status or a potentially poor response to oxidative stress.
36 THE AUTISM FILE | www.autismfile.com | info@autismfile.com
a poor response to oxidative stress. Many of the abnormalities in amino acid metabolism being screened for in the program represent the same markers that are recognized as abnormal in children who ultimately develop ASD. What we can’t determine, due to lack of scientific research, is if the abnormal levels of specific biomarkers found in children who currently have autism were present at the time of birth or in infancy. Based on current research at our institution and in other centers specializing in children with autism, we have reason to believe that the recognized amino acid concentration abnormalities in children with ASDs may have been present at birth and represent the genetic predisposition that defines the potential for autism development when environmental stressors are added to the equation. This will be the topic for a follow-up article. The state-mandated newborn screening program for metabolic core disorders has established reference ranges for only specific disease states; thus, reports are made only if the reference level is out of the defined range. For example, a disorder known as hypermethioninemia is only reported if the methionine levels are too high. It is widely known that many children with regressive autism present with hypomethioninemia (low levels of
ISSUE 33 2009
REPRINTED WITH PERMISSION © THE AUTISM FILE
Our hope is that autism will be redefined as a neuroimmune or epigenetic disorder with autistic regression as a symptom.
methionine). In addition, according to the Screening, Technology and Research in Genetics (STAR-G) project’s own literature, the amino acid disorder, hyperhomocysteinemia (too much homocysteine) is a disorder that can cause mental retardation and/or speech delays if left untreated. The recommended treatment is folic acid, B12, and B6 supplementation and a low methionine diet (no dairy or wheat)11 which is a recognized amino acid metabolic deficiency in some children with autism. In a study by Sarah Aldred, measured plasma amino acid levels in autistic patients, their siblings, and parents showed that children with ASD come from a family background of dysregulated amino acid metabolism, providing further evidence for an underlying biochemical basis for their condition12. In summary, it should be possible to retrospectively examine the amino acid concentrations of blood samples collected at birth in any state for abnormalities in amino acid biomarkers in children who were later diagnosed with regressive autism. The holy grail for medical care on the issue of vaccination safety is identifying a consistent biomarker or group of biomarkers that could indicate a compromised immune status or a potentially poor response to oxidative stress. Once recognized, a rapid, bedside test cartridge for these biomarkers could be developed for use prior to vaccinating the child. Additionally, a biomarker panel determination that a child could not safely be vaccinated according to the recommended vaccine schedule could reduce, if not eliminate, the need for parents to be questioned about medically-based vaccine exemptions. This biomarker panel would be valuable in states that do not allow religious or philosophical exemption from vaccines. We feel quite confident the identification of these biomarkers is close at hand. Pending the advancements in medical technology, parents are expected to vaccinate their children without question.
ISSUE 33 2009
References
1 CDC Web site, http://www.cdc.gov/ ncbddd/autism/overview.htm
The best advice that we can give them is to educate themselves before vaccinating their children and to consider the legal and ethical options available in their state. Newborn screening presents significant bioethical challenges. There is increased liability in the event of a false-positive or false-negative test, which can dramatically alter a course of treatment in congenital disorders. Most likely, many parents would not want their child to have a label of “autistic” at birth. In the age of personalized medicine, based on individual genomic differences, it will eventually be possible for every single individual to have a genetic profile performed at birth to assess genetic risk factors for certain diseases. For insurance reporting, the implications of genomic profiling are likely to cause many to fear discrimination by disease state, and this information is likely to be used to determine the cost of insurance coverage. We will probably need legislation to protect individuals from discrimination based on genomic profiling. We know certain individuals can smoke without developing lung cancer or emphysema, yet others, non-smokers even, develop smokingrelated diseases based on their genetic predisposition. There is growing research that we can change the way our genes are expressed with biomedical or dietary intervention, even if we cannot change our genes. In short, we should be discussing issues now. As there continues to be a surge in epigenetics (the codependent role of environment and genes) we will need to be proactive with the ethical issues surrounding our future generations. Our hope is that autism will be redefined as a neuroimmune or epigenetic disorder with autistic regression as a symptom. For parents of a child with autism, these ethical issues are of little concern when we discuss the possibility of recognizing risk factors at birth and preventing even one more case of autism … perhaps even staunching the epidemic.
NVAC Web site, http://www.hhs.gov/ nvpo/nvac/index.html
2
Generation Rescue Web site, http:// www.generationrescue.org/cases/ index.htm
3
Autism Omnibus Web site, http:// www.uscfc.uscourts.gov/omnibusautism-proceeding
4 5 Fourteen Studies Web site, http:// www.fourteenstudies.org/studies.html
James SJ et al., Metabolic biomarkers of increased oxidative stress and impaired methyllation capacity in children with autism. Am J Clin Nutr. 2004 Dec; 80(6):1611-7. http://www. ajcn.org/cgi/reprint/80/6/1611
6 7 Presentation on Autistic Enterocolitis, http://www.thoughtfulhouse. org/0405-conf-awakefield.htm
Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, Walker-Smith JA. Enterocolitis in children with developmental disorder. American Journal of Gastroenterology 2000;95:2285-2295
8 9 National Newborn Screening and Genetic Resource Center (NNSGRC) Web site: http://genes-r-us.uthscsa. edu/
The President’s Council on Bioethics Web site documents: http://www. bioethics.gov/reports/newborn_ screening/chapter3.html
10
http://www.bioethics.gov/reports/ newborn_screening/Newborn%20 Screening%20for%20the%20web.pdf The Screening, Technology and Research in Genetics (STAR-G) Project http://www.newbornscreening.info/ index.html
11 12 Aldred S. Plasma Amino Acid Levels in Children with Autism and Their Families, J Autism Dev Disord. 2003 Feb; 33(1): 93-7
REPRINTED WITH PERMISSION © THE AUTISM FILE
info@autismfile.com | www.autismfile.com | THE AUTISM FILE
37
