Guest guest Posted June 1, 2002 Report Share Posted June 1, 2002 I put together a few things I've collected that may help to connect some of the various theories. Remember that the Etiology of autism info from CPEA mentions immune abnormalities and genetic hotspots, especially on Chromosome 7. There are also similar related findings in other disorders. I guess there are alot of roads that can lead to a similar destination. To make it more interesting/confusing, there is even something on ABO bloodtype. I'm AB+ Source: University Of Southern California (http://www.usc.edu/) Date: Posted 3/20/2002 USC Researchers Define Role Of Protein, Discover Cause Of Chromosome Damage Pinpointing oxygen as the cause of routine chromosome damage and defining the role of a key protein in the repair of that damage are the subjects of two recently published papers from the laboratory of USC/Norris Comprehensive Cancer Center pathologist Lieber, the Rita and Polusky Chair in Basic Cancer Research at the Keck School of Medicine. The first paper was published in the March 5, 2002, issue of Current Biology; the other is slated for the March 22 issue of Cell, but was posted on the journal's Web site on March 1 as part of their " immediate early publication process. " The Cell paper, which will reportedly be on the cover of the March 22 issue, reveals that a protein previously linked to a devastating form of immunodeficiency plays a key role in a pathway by which nuclear DNA is repaired—the same system, in fact, which the immune system uses to create antibodies. About 15 percent of the cases of human severe combined immunodeficiency syndrome (known colloquially as the " bubble boy " disease) are caused by the mutation of a specific gene and its protein product. In April of 2001, a team of French researchers tracked down that gene, and named it and its product Artemis (after the Greek goddess for the protection of children); they had no idea at all, however, what kind of protein it was, nor what its function might be. Enter Lieber and graduate student Yunmei Ma. Lieber, Ma and their colleagues from the University of Ulm in Germany, conclusively demonstrated that Artemis is a key protein in the repair of double-stranded DNA breaks, a process called NHEJ (non-homologous DNA end joining). In the NHEJ pathway, explained Lieber, the ends of the broken DNA strands are trimmed and rejoined to one another. " What Artemis does is trim away the damaged parts of the DNA so that the strands can be joined, " said Lieber. Artemis and the NHEJ pathway are so essential, Lieber continued, that mice lacking NHEJ usually die at birth-and those that don't generally lack an immune system entirely and experience accelerated aging. And, as the previous studies have shown, humans with a defective Artemis protein also wind up without any immune defense to speak of. That, says Lieber, is because the immune system creates its defenses by cutting and then rejoining bits of nuclear DNA (the rejoining relies on NHEJ). Without Artemis, the cells can't create the antibodies necessary to go after the myriad pathogenic invaders we regularly encounter. Of course, being unable to cut and splice DNA can sometimes actually be of benefit. " What we're going to do next, " said Ma, the paper’s first author, " is try to screen for drugs that inhibit Artemis, because this might be useful from a cancer therapy standpoint. If we could just give a pulse of drug inhibitor for a while, we might be able to focus the effects of radiation therapy, for instance, by not allowing the cancer cells to repair themselves after being hit with the radiation. " Still, noted Lieber, for normal cells, Artemis and the NHEJ pathway are absolutely critical for survival. And that is because of how exquisitely vulnerable our cells are to DNA damage in the first place. Indeed, he said, all you have to do is take some cells out of the organism in which they live and look at them under a microscope, and you'll find that 5 to 10 percent of them will have at least one broken chromosome. Normally, of course, the NHEJ pathway works to fix those breaks. But the NHEJ pathway doesn't always function at full capacity. Indeed, a paper published by Lieber, M.D./Ph.D. student Zarir E. Karanjawala, and Norris Cancer Center researcher Chih-Lin Hsieh in 1999 found that in cells where the NHEJ pathway is disabled or missing, the number of cells with at least one chromosome break goes shooting up to 60 percent. What causes all this breakage? In the March 5 issue of Current Biology, Karanjawala, Lieber, and colleagues say it's the most ubiquitous of sources: oxygen. Originally, said Karanjawala, they had wondered if the damage might be coming from some environmental source, perhaps from background radiation. But when they began to look more closely, said Karanjawala, they found it was in the very air we breathe. " It's coming from the oxygen, " Karanjawala explained. " We found that if you vary the oxygen levels in which cells are grown, the breakage levels of the chromosomes vary as well––the higher the oxygen level, the more breakage you'll see. " The oxygen causes its damage, Lieber said, through oxidative free radicals—highly reactive atoms with an unpaired electron that can rip through our cells " like a bullet. " " Our bodies are being riddled with these bullets every day, " explained Lieber, " whether we like it or not. And the sorts of double-strand DNA breaks we were looking at are hard to repair. Even if you put the two ends together the best you can, you usually lose a couple of nucleotides along the way. And so every time we get an oxidative free radical hit, which happens several times per day per cell, we lose a little info. Every time it hits your DNA, you wind up with a little less genetic information than you had when you started the day. " The solution? ly, said Lieber, there may be none. " Oxygen—can't live with it, can't live without it, " he commented. " We need it to survive, but ultimately, it's also probably what kills us. " -------------------------------------------------------------------------------- Note: This story has been adapted from a news release issued by University Of Southern California for journalists and other members of the public. If you wish to quote from any part of this story, please credit University Of Southern California as the original source. You may also wish to include the following link in any citation: http://www.sciencedaily.com/releases/2002/03/020313075022.htm ---------------------------------------------------------------------- Source: University Of Michigan Health System (http://www.med.umich.edu/) Date: Posted 5/15/2002 Parasite Or Partner? Study Suggests New Role For Junk DNA ANN ARBOR, Mich. – Junk DNA is the Rodney Dangerfield of the genetics world. It makes up nearly half of all human DNA, but many scientists dismiss it as useless gibberish. A new study published online today from the June 2002 issue of Nature Genetics, however, suggests that segments of junk DNA called LINE-1 elements deserve more respect. Conducted by scientists from the University of Michigan Medical School and Louisiana State University, the study is the first to show in mammalian cells that some human LINE-1, or L1, elements can jump to chromosomes with broken strands of DNA, slip into the break and repair the damage. “Transposable L1 elements make up 17 percent of our DNA, but very little is known about them,” says V. Moran, Ph.D., an assistant professor of human genetics and internal medicine in the U-M Medical School, who developed the first assay to identify mobile L1s in the human and mouse genomes. “Until now, everyone thought L1s were just intracellular parasites in our DNA – leftovers from the distant evolutionary past. The big question in the field is: Are they still there because we can’t get rid of them or do they have a function?” L1s “reproduce” by using RNA and a process called reverse transcription to make complementary DNA copies of themselves, which can jump into other DNA sequences. Normally, L1s use an enzyme called endonuclease to cut the genetic DNA and create a space, so they can plug themselves into the genome. “We knew about the endonuclease pathway,” says Tammy A. h, a U-M graduate student in human genetics and first author of the paper. “But we didn’t know there was another mechanism that didn’t require endonuclease, or that L1s could jump into existing breaks in DNA.” h tested human L1s’ ability to repair DNA breaks in several normal and DNA-repair mutant cell lines derived from Chinese hamster ovary cells. Other researchers had demonstrated the ability of human L1s to repair DNA breaks in yeast cells, but h is the first to show the effect can occur in mammalian cells. Since DNA damage may lead to cell death unless it is repaired, the existence of an alternate repair pathway could be a good thing for the host cell. The question is, what’s in it for the L1? “This study brings up the question of whether L1s are just taking advantage of DNA breaks to plug themselves into these sites or are they are being used by the host cell to mediate the repair,” says Moran. “From the L1s’ point of view, this gives it an alternate way of integrating into the DNA.” Because L1s are so ancient and because they sometimes carry segments of genes with them when they jump to a new location, Moran believes they have played an important role in human evolution by increasing genetic diversity. He is one of only a few scientists to study L1s in the human genome. “We have more transposable L1s in the human genome than any other species, but we know the least about where and how they move in humans,” says Moran. “We are here today either because of, or in spite of, L1s.” In future research, Moran’s research team will examine whether it is possible to direct L1s to repair specific breaks in DNA, whether L1s can be used as vectors to deliver genetic material to specific DNA locations, and the impact of an L1 insertion on genes. U-M researchers in the study were supported by the M. Keck Foundation and the National Institutes of Health. Gilbert, Ph.D., a U-M post-doctoral fellow in human genetics, collaborated in the study. Other collaborators included Mark A. Batzer, S. Myers, and Bethaney J. from Louisiana State University; D. Stamato from Lankenau Institute for Medical Research in Wynnewood, Penn.; and Guillermo E. Taccioli from Boston University’s School of Medicine. Editor's Note: The original news release can be found at http://www.med.umich.edu/opm/newspage/2002/junkdna.htm ----------------------------------------------------------------------- (MY NOTE-some of you may remember the research on Gulf War Illness where there were findings of DNA in the blood and mention of this chromosomal area) THYROID AUTOANTIGEN, 70-KD; G22P1 Alternative titles; symbols Ku ANTIGEN, 70-KD SUBUNIT; Ku70 LUPUS AUTOANTIGEN p70 THYROID-LUPUS AUTOANTIGEN; TLAA Gene map locus 22q11-q13 The G22P1 gene encodes subunit p70 of the p70/p80 autoantigen. The p70/p80 autoantigen consists of 2 proteins of molecular mass of approximately 70,000 and 80,000 daltons that dimerize to form a 10 S DNA-binding complex. See 194364 for discussion of the gene encoding the p80 subunit. Exchange of immunologic reagents showed that the p70/p80 autoantigen is identical to the Ku antigen, the Ki antigen, and the 86- to 70-kD protein complex. The p70/p80 complex binds to the ends of double-stranded DNA in a cell cycle-dependent manner, being associated with chromosomes of interphase cells, followed by complete dissociation from the condensing chromosomes in early prophase. Both p70 and p80 contain phosphoserine residues. A role for the antigen in DNA repair or transposition has been proposed. Taccioli et al. (1994) showed through genetic and biochemical approaches that the XRCC5 is the 80-kilodalton subunit of the Ku protein. Ku binds to free double-stranded DNA ends and is the DNA-binding component of the DNA-dependent protein kinase. Thus, the Ku protein is involved in DNA repair and in V(D)J recombination, and the Ku-DNA-dependent protein kinase complex may have a role in those same processes. ------------------------------------------------------------------------ EMBO J 2002 Apr 15;21(8):2038-44 Related Articles, Books, LinkOut Specific interaction of IP(6) with human Ku70/80, the DNA-binding subunit of DNA-PK. Hanakahi LA, West SC. Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK Corresponding author e-mail: stephen.west@... In eukaryotic cells, DNA double-strand breaks can be repaired by non-homologous end-joining, a process dependent upon Ku70/80, XRCC4 and DNA ligase IV. In mammals, this process also requires DNA-PK(cs), the catalytic subunit of the DNA-dependent protein kinase DNA-PK. Previously, inositol hexakisphosphate (IP(6)) was shown to be bound by DNA-PK and to stimulate DNA-PK-dependent end-joining in vitro. Here, we localize IP(6) binding to the Ku70/80 subunits of DNA- PK, and show that DNA-PK(cs) alone exhibits no detectable affinity for IP(6). Moreover, proteolysis mapping of Ku70/80 in the presence and absence of IP(6) indicates that binding alters the conformation of the Ku70/80 heterodimer. The yeast homologue of Ku70/80, yKu70/80, fails to bind IP(6), indicating that the function of IP(6) in non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian end-joining process. PMID: 11953323 [PubMed - in process] Mutagenesis 2002 May;17(3):193-200 Related Articles, Books, LinkOut Environmental factors affecting transcription of the human L1 retrotransposon. I. Steroid hormone-like agents. Morales JF, Snow ET, Murnane JP. Radiation Oncology Research Laboratory, University of California-San Francisco, 1855 Folsom Street, MCB 200, San Francisco, CA 94103, USA and Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway, Burwood, 3125 , Australia. The L1 retrotransposon has significantly shaped the structure of the human genome. At least 30% of human genome sequence can be attributed to L1 reverse transcriptase activity. There are 10(5) copies of the human L1 retrotransposon, L1Hs, most of which are defective, although approximately 8-9x10(3) are full length. L1Hs elements transpose through an RNA intermediate and transcription is thought to be the rate limiting step in retrotransposition. Because transcription of retrotransposons in a variety of organisms has been shown to respond to environmental stimuli, we investigated the influence of various agents on transcription from two different L1Hs promoters. The activity of the L1Hs promoters was analyzed by transfecting L1Hs-expressing cell lines with plasmids containing the L1Hs promoters fused to the LacZ reporter gene and monitoring expression with a beta-galactosidase assay. Small increases in beta-galactosidase activity were observed with both L1Hs promoters after treatment with serum, testosterone, dihydrotestosterone and organochloride pesticides, indicating that these agents can influence L1Hs transcription. PMID: 11971989 [PubMed - as supplied by publisher] J Mol Evol 1999 Jun;48(6):675-83 Related Articles, Books, LinkOut Comparison between two human endogenous retrovirus (HERV)-rich regions within the major histocompatibility complex. Kulski JK, Gaudieri S, Inoko H, Dawkins RL. Centre for Molecular Immunology and Instrumentation, University of Western Australia, Faculty of Medicine and Dentistry, P.O. Box 5100, Canning Vale, 6155, Western Australia, Australia. jkulski@.... Sixteen human endogenous retrovirus (HERV) sequences were detected within 656 kb of genomic sequence obtained from the alpha- and beta-block of the class I region of the major histocompatibility complex (MHC). The HERVs were identified and characterized as family members of HERV-16 (11 copies), HERV-L (1 copy), HERV-I (2 copies), HERV-K91 (1 copy), and HARLEQUIN (1 copy) by sequence comparison using CENSOR or Repeat Masker, BLAST searches, and dot plots. The 11 copies of HERV-16 arose as products of duplication of genomic segments containing HLA class I (HLAcI) and PERB11 (MIC) genes inter alia, whereas the other five HERVs arose after duplication probably as a consequence of single insertion events or translocations. HERV-L and HERV-I are located between the duplicated genes PERB11.2 (MICB) and PERB11.1 (MICA), and HLA-B and HLA-C, respectively, whereas HERV-K91 and HARLEQUIN are located telomeric of HLA-C. A highly fragmented copy of HERV-I was also found telomeric of PERB11. 4. Structural analysis of open reading frames (ORFs) revealed the absence of intact coding sequence within the putative gag, pol, and env gene regions of all the HERVs with the exception of HERV-K91, which had two large ORFs within the region of the putative protease and pol genes. In addition, the 5'-LTR of HERV-L contained a 2.5-kb element that was AT-rich and large ORFs with putative amino acid sequences rich in tyrosines and isoleucines. HERV-I, HARLEQUIN, and at least four copies of HERV-16 appear to have been receptors for the insertion of other retrotransposons including Alu elements and fragments of L1 and THE1. Examination of flanking sequences suggests that HERV-I and HERV-L had occurred by insertion into ancient L1 fragments. This study has revealed that the alpha- and beta-block region within the MHC is rich in HERV sequences occurring at a much higher ratio (10 to 1) than normally observed in the human genome. These HERV sequences will therefore enhance further studies on disease associations and differences between human haplotypes and primates and their role in the evolution of class I genes in the MHC. PMID: 10229571 [PubMed - indexed for MEDLINE] Cell Mol Biol (Noisy-le-grand) 2002 Mar;48(2):213-7 Related Articles, Books, LinkOut The HERV-W/7q family in the human genome. Potential for protein expression and gene regulation. Alliel PM, Perin JP, Goudou D, Bitoun M, B, Rieger F. INSERM U-488, Batiment Pincus, Le Kremlin-Bicetre, France. alliel@... A new family of human endogenous retroviruses has recently been discovered. The best known example of a full length member of this family, HERV-W/7q, is located on chromosome 7. HERV-W/7q is characterized by a long open reading frame within its env gene which is expressed in various tissues, and mainly in placenta, as a protein that we called enverin. A search for new retroviral sequences related to the HERV-W/7q family allowed the characterization of such elements in chromosome 6. A novel full length HERV with an env gene of the HERV-W/7q type, potentially encoding a truncated form of enverin has been identified on chromosome 10. The distribution of HERV-W/7q related sequences close to or within genes offers the possibility that the expression of these genes may be regulated by their companion retroviral sequences. PMID: 11990458 [PubMed - in process] Neurovirol 2000 May;6 Suppl 2:S67-75 Related Articles, Books, LinkOut Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a 'chain-reaction' triggered by infectious agents in multiple sclerosis? Perron H, Perin JP, Rieger F, Alliel PM. BioMerieux STELHYS, Chemin de l'Orme, 69280 Marcy l'Etoile, France. Different groups have observed retrovirus particle (RVP) production in cell cultures from patients with multiple sclerosis (MS). This in vitro production appeared relatively specific for MS versus healthy controls, but was likely to be enhanced or activated by infectious triggers such as Herpesviruses (e.g. HSV, EBV). Independent molecular analysis of retroviral RNA associated with RVP revealed two different genetic families of endogenous retroviral elements (HERV): MSRV/HERV-W and RGH/HERV-H. Interestingly, these sequences were detected by mutually exclusive primers in RT - PCR amplifications. Surprisingly, these two HERV families both contain an ancestral proviral copy inserted in chromosome 7q21-22 region at about 1 kb of distance of each other. Another HERV-W proviral sequence is located within a T-cell alpha-delta receptor (TCR) gene in chromosome 14q11.2 region. Interestingly, these two regions correspond to genetic loci previously identified as potentially associated with 'multigenic' susceptibility to MS and TCR alpha chain genetic determinants have been reported to be statistically associated with MS. A plausible role for infectious agents triggering a co-activation of the chromosome 7q HERV tandem (replicative retrovirus and/or other virus and/or intracellular bacteria) and, eventually, other HERV copies, is discussed. The role of particular HERV polymorphism and the production of pathogenic molecules (gliotoxin and superantigen) possibly associated with retroviral expression are also evoked. An integrative concept of pathogenic 'chain-reaction' in MS involving several step-specific pathogenic 'agents' and 'products' somewhat interacting with particular genetic elements would federate most partial data obtained on MS, including retroviral expression. Publication Types: Review Review Literature PMID: 10871789 [PubMed - indexed for MEDLINE] Int J Mol Med 2002 Mar;9(3):207-12 Related Articles, Books, LinkOut Schizophrenia: a genetic perspective (review). Shastry BS. Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA. Barkur@... Schizophrenia is a complex neurodevelopmental disorder characterized by mental dysfunction across multiple domains of the brain. It affects 1% of world's general population and the nature of neurobiological lesions in the schizophrenic brain are not known. Although the exact etiology of the disorder is not understood, twin, family and adoption studies have provided consistent evidence that genetic factors play a major role in the pathogenesis. A genome-wide genetic linkage screen identified loci on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 22 and the X with positive lod scores, thus excluding a single major locus for schizophrenia. Association studies have generated disappointing results in identifying the susceptible DNA sequence variants and the anticipation hypothesis on trinucleotide repeat expansion provided equivocal results or lack of enthusiasm. Although there are no biological markers at present, the recent finding that human endogenous retrovirus is activated in cerebrospinal fluid as well as in the postmortem schizophrenic brain may change our understanding of the etiopathogenesis of this disease. Meanwhile, treatment with newly developed anti-psychotic drugs combined with educational and cognitive rehabilitation procedure may help the patients to cope with the illness. Publication Types: Review Review, Tutorial PMID: 11836624 [PubMed - indexed for MEDLINE] Mol Psychiatry 2001 Nov;6(6):634-46 Related Articles, Books, LinkOut Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms. Pearce BD. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Dr WMB-4000, Atlanta, GA 30322, USA. bpearce@... The task of defining schizophrenia pathogenesis has fascinated and frustrated researchers for nearly a century. In recent years, unprecedented advances from diverse fields of study have given credence to both viral and developmental theories. This review considers possible mechanisms by which viral and developmental processes may interact to engender schizophrenia. Many of the current controversies in schizophrenia pathogenesis are reviewed in light of the viral hypothesis, including: epidemiological findings and the role of a genetic diathesis, phenotype heterogeneity, abnormalities in excitatory and inhibitory neurotransmitter systems, anomalous cerebral latereralization, and static vs progressive disease. The importance of animal models in elucidating the impact of viral infections on developing neurons is illustrated by recent studies in which neonatal rats are infected with lymphocytic choriomeningitis virus in order to examine alterations in hippocampal circuitry. Finally, consideration is given to a new hypothesis that some cases of schizophrenia could be instigated by a viral infection that disrupts developing inhibitory circuits, consequently unleashing glutamatergic neurotransmission leading to selective excitotoxicity, and a degenerative disease course. Publication Types: Review Review Literature PMID: 11673791 [PubMed - indexed for MEDLINE] Blood 2002 Apr 1;99(7):2477-82 Related Articles, Books, LinkOut Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement. Preece AF, Strahan KM, Devitt J, Yamamoto F, Gustafsson K. Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. No definitive biologic function has been associated with the human ABO histo-blood group polymorphism, or any other terminal carbohydrate differences within or between closely related species. We have experimentally addressed the question of whether viral particles can become glycosylated as determined by the glycosylation (eg, ABO) status of the producer cell and as a result be affected by human serum containing specific natural antibodies (NAbs). Measles virus was produced in cells transfected with cDNA encoding, either human A-transferase, B-transferase, an inactive " O-transferase, " or a pig alpha1-3galactosyltransferase (alpha1-3GT) synthesizing the Galalpha1-3Gal structure. The viruses were shown to carry the same ABO structures as the cells; that is, A but not B if produced in A-type cells, and B but not A if produced in B-type cells. Only O was detected on the virus produced from O-type cells, whereas reduced amounts of O appeared on the A- and B-type viral particles. In addition, the Galalpha1-3Gal structure was transferred onto measles only when grown in human cells expressing this structure. When subjected to human preimmune sera, the A-type, the B-type, and the Galalpha1-3Gal viral particles were partially neutralized in a complement-dependent manner. However, the O-type or the Galalpha1-3Gal-negative viral particles were not neutralized. The neutralization appeared to be mediated by specific NAb, as judged by specific inhibition using synthetic A and Galalpha1-3Gal oligosaccharides. Such viral glycosylation may thus partly explain why the ABO antigens and other similar intraspecies as well as interspecies polymorphic carbohydrates have evolved and been maintained over long evolutionary periods. PMID: 11895782 [PubMed - indexed for MEDLINE] _________________________________________________________________ Join the world’s largest e-mail service with MSN Hotmail. http://www.hotmail.com Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 3, 2002 Report Share Posted June 3, 2002 A consistency in the genetic studies of autism also reveal a clear connection to the CYP 450 enzymes. Therefore the lutein theory as a causal factor for autism identifies the source of the intensified free radical production. 1p Defects of chromosome 1p include: Cytochrome P450: CYP2J2 arachidonic acid epoxygenase deficiency; CYP4B1 Parkinsonism. Porphyria cutania tarda, light sensitive dermatitis and associated excresion of uroporphyrin; hypertrichosis and hyperpigmentation also occur. Waardenburg syndrome (WS) type 2B sensorinural hearing loss, heterochromia irides, white forelock and early graying. Oligodendrogliomas: 5 2q Defects of chromosome 2q include: Cytochrome P450: Cyp27 (Sterol 27-hydroxylase): ?bile acid synthesis? and cerebrotendinous xanthomatosis, cerebral cholesterinosis (CTX). Waardenburg syndrome (WS): an inherited disorder often characterized by varying degrees of hearing loss and changes in skin and hair pigmentation: 6q Defects of chromosome 6q include: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis caused by mutations in the steroid 21-hydroxylase gene (CYP21) in more than 90% of affected patients. Retinitis Pigmentosa (RP) also found on chromosomes 1p, 1q , 9q and 10p. 97, 8, 37 A clotting of the pigment in the choroid structure of the eye. Retinitis pigmentosa is reported in more than a coincidental number of families (parent or grandparent) who have a child or grandchild with autism.85, 86, 91 ?Immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6?. 108 IgA deficiency has been reported in autism. 99 [NB: 6p and 10p: Refsum?s disease (treatment with a chlorophyll free diet ? Eldjarn, L. et al 1966) is characterized as a syndrome with RP and nerve deafness, ichthyosis, cerebellar ataxia and polyneuritis.] 7q Defects of chromosome 7q include: Cytochrome P450: Nitric Oxide Synthase 3 (NOS3), endothelial nitric oxide synthase (ENOS). ?The unexpected recognition of the substrate L-arginine at the H4B (tetrahydrobiopterin) site indicates that this site is poised to stabilize a positively charged pterin ring and suggests a model involving a cationic pterin radical in the catalytic cycle? Raman et al (1998); CYP3A4, CYP3A43 ?Xenobiotic? metabolism; CYP51, sterol biosynthesis, cholesterol biosynthesis; CYP5, thromboxane A synthase, bruises, nosebleeds, defective platelet aggregation. Speech Language disorder (also occurring on 19q and 16q). Hemochromatosis (HFE3); 12, 13, 14, 36 a disorder due to deposition of hemo-siderin in the parenchymal cells, causing tissue damage and dysfunction of the liver, pancreas, heart, and pituitary. Other clinical signs include bronze pigmentation of the skin, arthropathy, diabetes, cirrhosis, hepatosplenomegaly, hypogonadism, and loss of body hair. Idiopathic Hemochromatosis: an autosomal recessive disorder of iron metabolism associated with a gene tightly linked to the A locus of the HLA complex on chromosome 6.58 Hemochromatosis is also linked to Crystal Deposition Disease: ?CPPD crystal deposition disease may be classified as hereditary (autosomal dominant), sporadic (idiopathic), or associated with other metabolic diseases, such as hyperparathyroidism, hemochromatosis, hypothyroidism, or even gout itself. The acute pseudogout syndrome is characterized by an abrupt onset of acute inflammatory gout-like arthritis affecting one or more joints, most commonly the knee. Among other clinical manifestations, about 50% of patients with CPPD deposit disease present with progressive degeneration of multiple joints, usually the knees, ankles, wrists, elbows, hips, or shoulders. The initiating event for CPPD crystal deposition within joints is not well understood. The pathogenesis of the acute inflammatory changes in the joints are attributed to the uptake of CPPD crystals by polymorphonuclear and mononuclear phagocytes, followed by release of degradative enzymes, inflammatory mediators, and chemotactic factors, very much as in gouty arthritis.? 73 In the autist, the typical presentation of these iron deposition disorders is not found. Nevertheless, autists do often have problems with iron metabolism, and even when anemic, supplementing with iron can result in an unexpected drop in iron level. Likewise, supplementing with Vitamin C has an unexpected negative outcome in some autists. [NB: Vitamin C Toxicity: ?Megadoses of vitamin C of 1000-2000 mg have commonly been associated with gastrointestinal disturbances (nausea, abdominal cramps and diarrhea). In general, megadoses of vitamin C should be avoided in individuals with a history of renal stones due to oxalate formation or hemochromatosis or other diseases related to excessive iron accumulation. Excess vitamin C may predispose premature infants to hemolytic anemia due to the fragility of their red blood cells. In healthy individuals, it appears that megadoses of vitamin C are well tolerated and not associated with any consistent adverse effects.? 82, 77, 72 Vitamin C supplementation in excess of the RDA is not always a good idea for people with ASD.] 13q Defects associated with chromosome 13q include: ?s disease (potentially resulting in jaundice), copper-transporting P-type ATPases copper transport, Mutations of ATP7B. Currently NIH is funding studies to clarify the association between ?s disease and autism. In our experience we have encountered an autistic female who presented with yellow eyes and also encountered many ASD females who exhibited yellow eye color especially at or near the onset of menstruation. Phylloid pattern of pigmentary disturbance (Ribeiro Noce T et al). Hirschsprung disease type 2: Puffenberger et al. (1994) presented evidence that Hirschsprung disease type 2 (HSCR2; 600155), an apparently multigenic disorder, is due to mutation in the endothelin-B receptor gene. EDNRB was a candidate gene because it mapped to the same region of chromosome 13 as did HSCR2. Among the Mennonites, at least 5 megacolon patients did not seem to carry the specific EDNRB mutation trp276 to cys (W276C) present in most of the affected members. This suggested the existence of as yet undiscovered HSCR susceptibility genes. Among the affected Mennonites, HSCR was associated with nonenteric phenotypes in several: bicolored irides (6.3%), hypopigmentation (2.5%), sensorineural hearing loss (5.1%), and white forelock (7.6%), reminiscent of the Shah-Waardenburg syndrome [see also 22q] Puffenberger et al. suggested that these nonenteric features represented pleiotropic effects of the W276C mutation. This and other findings indicated that interaction of EDN3 with the endothelin-B receptor is essential to the development of neural crest-derived cell lineages.4 16p [The values given for 16p (IMGSAC 1999 1.51, pe et al. 1998 0.74) are scores below 3 but is in a region cited in more than one study.] Defects associated with chromosome 16p include the differential diagnosis of the guttate leukoderma of TSC (Tuberous Sclerosis), also found on chromosome 9q and includes several clinical entities such as idiopathic guttate hypomelanosis, 18 disseminated hypopigmented keratoses, and dyschromic amyloidosis. 8, 9, 10, 11 18q Defects associated with chromosome 18q include Erythropoietic Porphyria. B-Cell CLL/Lymphoma (unknown inhibitor of apoptosis) dominant white-spotting; ?B-cell lymphomas and polyclonal B-cell lymphoproliferative disorders are related to Epstein-Barr virus (EBV) activation.?83 19p Defects of chromosome 19p include: Cytochrome P450: CYP4F3, Leukotriene B4 omega-hydroxylase (LTB4H) bioactive compounds that play roles in such processes as inflammation. Fucosyltransferase deficiency (co-occurring condition - enzyme deficiencies) potentially relating to purine and pyrimidine biosynthesis. Oligodendrogliomas (tumors associated with ataxia, visual impairment and seizures) 5, 6 [see also 1p] Regions not cited in the whole genome studies but with literature to support the connection to ASD: Chromosome 15 ?The strength of evidence supporting claims of a specific association between genetic /chromosomal disorder and ASDs is very variable. The strongest evidence of a causal association is found for tuberous sclerosis, fragile X and inverted duplications of chromosome 15. While fragile X Syndrome used to be thought to affect as many as 25% of males with ASDs, Fombonne, in his review estimated a far lower figure (0.75%).The symptoms shown by those with this disorder may be more properly described as ?autism like? or fitting only within the broader spectrum. An association between duplications and triplications of part of the long arm of chromosome 15 of maternal origin has been found with ASDs, often accompanied by severe mental retardation. This is of some interest as genetic studies of ASD have identified loci on the long arm of Chromosome 15. The role of mental retardation in the association needs to be investigated. In addition, sex chromosome abnormalities ( syndrome) have been linked to ASDs. Some 5% of females with syndrome have either ASDs or features that may fall within the broader ASD phenotype. In all confirmed cases the normal X chromosome was maternal in origin. It is possible that there is increased vulnerability to ASDs in females who lack a normal paternally derived X-chromosome. Untreated phenylketonuria is nowadays so rare that the evidence for an association stems from very early studies that were undertaken before the use of well-developed and validated diagnostic criteria, although the evidence from the early reports is quite persuasive. The frequency of single gene disorders or chromosomal abnormalities in population based and clinic samples of individuals with ASDs is low and amounts to at most 5-10% of the population.? 1 Additional defects associated with chromosome 15 include: Cytochrome P450 ?aldehyde dehydrogenase?, ?retinaldehyde dehydrogenase 2?. Chromosome 15 syndrome of inv dup (inversion-duplication): Macrogenitalia, seizures, autism. 80 15q Defects associated with chromosome 15q include: Cytochrome P450 ?molybdenum cofactor deficiency? molybdenum cofactor is essential to the function of 3 enzymes: sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Molybdenum cofactor (molybdopterin) deficiency is characterized by developmental delay, seizures, lens dislocation and often early infantile death; CYP19: ?estrogen synthetase?, induced by follicle stimulating hormone; CYP450 ?polycystic ovary syndrome?; CYP1A2 (deficiency: porphyria cutania tarda); CYP11A, cholesterol side chain cleavage; CYP1A1: (XRE?s) xenobotic response elements. Oculocutaneous albinism type 2 (OCA2), ?Xanthism type (OCA3) found on chromosome 9q?, [?The P protein, with 12 transmembrane domains localized to the melanosome, has no assigned function as of yet but is responsible for OCA2 when dysfunctional?3] pink protein, melanosomal membrane. 30, 35, 38, 40, 42, 43 Angelman ?light pigmentation? and Prader-Willi characterized by obesity, round face, almond shaped eyes, obsessive compulsive eating and often with scratching and itching. 4q Defects associated with chromosome 4q include Cytochrome P450 ?Circadian Locomotor Output Cycles Kaput? CLOCK (Steeves et al 1999). Piebaldism c-kit receptor: congenital patches of white skin and white hair, principally located on the scalp, forehead, chest and abdomen and on the limbs; several patients report lifelong severe constipation. 23 We have within our case histories an adult male age 40 who was diagnosed with Down Syndrome, ASD and piebaldism. He was quite high functioning and generally healthy. He did exhibit the characteristic self-limited diet of the Down syndrome- ASD group. His diet mainly consisted of pork sausages, mashed potato, fruit yogurt, wheatabix cereal with milk, hot tea with milk and occasionally mashed cauliflower, fish or chocolate. When hungry enough he could be coerced into eating the mashed potato with pureed vegetable (usually peas, carrots or broccoli). After these meals he would become withdrawn and complain of headache this might be followed by a period of 1 or more days when he would refuse food altogether. He was childlike and mildly mischievous. He attended some special college courses, participated in some social activities and was adapting to a supported living arrangement. His medical history was conspicuously lacking any reference to other medical conditions which often co-occur with Down syndrome. He also had the wide gap between the first and second toes (big toe and long toe) characteristic for Down Syndrome 111 and prevalent in autism. Twenty nine of the 35 children we saw in India had this wide gap between the toes. 10q Defects associated with chromosome 10q include: Cytochrome P450: (RBP) retinal-binding protein; CYP2E (ethanol-inducible P450); CYP45026A2, CYPP450RAI2 (retinoic acid inactivating) capable of converting all-trans RA to polar metabolites. Retinoic acid (RA) plays an important role in regulating gene expression during embryonic development; CYP2C19, mephenytoin-4-Pime-hydroxylase; CYPC17, ?congenital adrenal hyperplasia? due to 17-alpha hydroxylase deficiency; CYP2C9, CYP2C8, CYP2C18 (gene expression). Oligodendrogliomas ?pterin-4-alpha-carbinolamine dehydratase? (PCBD) leads to mild PKU ?hyperphenylalaninemia?, hyperphenylalaninemia with premapterinuria (increased ratio of neopterin to biopterin). Hermansky Pudlak syndrome: Hermansky-Pudlak Syndrome (HPS) is a genetic metabolic disorder which causes albinism, visual impairment, a platelet dysfunction with prolonged bleeding, and progressive symptoms including pulmonary fibrosis, inflammatory bowel disease and kidney disease. The severity of HPS ranges from very mild with few symptoms to severe and disabling., membrane protein lysosome/melanosome structure/function. Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. 16 17q Defects associated with chromosome 17q include: café-au-lait macules (co-ocurring condition ? asthma); 2, 46 Café-au-lait macules are commonly reported by parents among the many types of pigment anomalies described for ASD children. Autosomal dominant retinitis pigmentosa (ADRP) (Inglehearn CF et al). Sanfilippo (sulfate sulfatase deficiency and sulfamidase deficiency). Chromosome 21, (not included in the genome screen cited in the table) Down Syndrome (trisomy 21) is estimated by the University of Goteberg, Sweden, to co-occur with ASD at 5 to 9% and by Kennedy Kreiger at 5 to 7 % which also cites Down Syndrome co-occurring with epilepsy at 10%. 92, 93 These figures, rarely cited in the literature, indicate that as many as 2% of the autism population also have Down syndrome. 22q Defects associated with chromosome 22q include: Cytochrome P450: ?peroxisome proliferator-activated receptor-alpha?(PPARA); CYP2D, ?xeno-biotic metabolism?, ?thyroid-lupus autoantigen?; CYP3A7, ?Polypeptide 7?, CYP3A5 gene constitutes the major genetic determinant of polymorphic activity in humans. (ussen, A et al, 2000). Adenylosuccinate lyase deficiency. Waardenburg-Shah Syndrome: Dystopia canthorum (lateral displace-ment of the inner canthus of each eye) Pigmentary abnormalities of hair, iris, and skin (often white forelock and heterochromia iridis); Sensorineural deafness. The combination of recessively inherited WS type II characteristics with Hirschsprung disease has been called Waardenburg-Shah syndrome or WS type IV, SRY-box containing gene 10 transcriptional activator, Mutations of SOX10. Hearing impairment. 27, 41, 86 See also 2q (Hirschsprung is also associated with chromosome 13 and 20) Xp Defects of chromosome X include: Cytochrome P540 ?granulomatous disease?, chronic CGD (lack of metabolic burst). Ocular albinism type 1, G-protein-coupled receptor signal transduction Mutations of OA1, pinkeyed-dilution (p). 30, 32, 68 Incontinentia pigmenti (IP) (usually lethal prenatally in males): 9 ?We show the complications observed in a large series of children with Hypomelanosis of Ito (HI) or incontinentia pigmenti achromians, studied in a neurology service over 30 years. Of the 76 patients, 35 were male (46%) and 41 female (54%) with ages ranging from newborn to 10 years at the time of the first visit. Mental retardation was observed in 43 cases (57%) of whom eight (10%) showed autistic behavior; 16 (21%) were borderline and only 17 (22%) had a normal mental level (IQ > 85). Thirty-seven patients (49%) had seizures, consisting of infantile spasms in six cases (8%). Twelve cases showed macrocephaly and coarse facies, six had microcephaly, and 14 showed hypotonia with pes valgus and genu valgus. Three cases of cerebellar hypoplasia, another of intracranial arteriovenous malformation and another of distal spinal muscular atrophy were observed as well. Some other anomalies, such as syndactyly, clinodactyly, abnormalities of the skeleton, asymmetry of the facies, ears, body and/or extremities, gynecomastia and asymmetrical breasts, short stature, oral alterations, congenital cardiopathies and genital anomalies, were also occasionally found. Three children died, but necropsy was performed only in one. Anatomical and histological studies did not disclose specific findings.? 17 ?It is suggested that skin changes indicating underlying neurocutaneous disorders be meticulously looked for in all cases with autism and autistic-like conditions.? 21 ?Subcellular defects of hypomelanosis in tuberous sclerosis (TS) (28 subjects) were compared by light and electron microscopy with other forms of congenital circumscribed hypomelanosis that occur in nevus depigmentosus (ND) (8 subjects) and in piebaldism (PB) (4 subjects), respectively.? 22 ?Embryologic migration of both melanoblasts from neural crest and cortical neurons occurs in the second trimester, suggesting a common mechanism for the developmental pathology of skin and brain.? 24 Four adjacent loci, C4A, 21-OHA, C4B, and 21-OHB located in the class III region of the major histocompatibility complex (MHC). In this region, known as the hypervariable region or the mitochondrial DNA region, the 21-OHB gene is generally inactive. The C4A gene abnormalities are reported to be more common in the parents of autistic offspring and particularly the mothers. The C4B gene null allele is more frequent in the autism population and appears to increase immune reactivity to viral pathogens, toxins, molds, pollens and other hapten substances. The immune system evolution to include plant pigments as pathogens has likely been exacerbated by the use of plant substance in vaccines. Likewise, there is evidence that the autistic population cannot make enzymes from plant foods in the normal way. In the human body bacteria such as e-coli, candida and fungi species produce these substances (carotenoids) for us. As humans we have evolved to include in our gut flora species such as lacto bacillus acidophilus (dependant on lactose, milk sugar) for some of our vitamin manufacture (particularly some B vitamins). In earlier human history it is not reasonable to expect that humans required lactobacillus acidophilus because milk was not regularly consumed other than in infancy through breastfeeding which primarily provides bifidus. It appears that people who have anomalies among these four adjacent loci are the population referred to as having immune system disorders. Offspring from families who have these anomalies have a greater chance of being diagnosed with autism. It also appears that in autism, enzyme deficiencies without any corresponding genetic anomaly is a prevalent finding. In the human body, Cytochrome P450 is involved in the manufacture of enzymes and is strongly influenced by Fe2+ ascorbate (Iron + Vitamin C). The breakdown products from plant foods particularly carotenoids, are used for the formation of mevalonic acid in a normal metabolism, which in turn is used in the regulation of cholesterol. Cholesterol is the primary regulator of hormones. In autism Cytochrome P-450 enzymes are deregulated as the immune system removes the pigment component and releases the other plant by-products. This interference or regulation of pigments by the immune system results in changes in the body of an autist which we see as enzyme deficiencies, allergic reactions, skin pigmentation anomalies, dermatological irregularities, digestive problems, nutrient imbalance, gut dysbiosis, metabolic imbalance. Thus autism can be called a disorder of mitochondrial DNA, an immuno-genetic condition, an inborn error of metabolism, or a pigmentary disorder. NADPH P-450 is required for the breakdown and conversion of pterins (pigments). In autism, some of these pigments are being engulfed by immune macrophages and the conversion process is disrupted. This results in findings such as elevated levels of neopterin and biopterin in the urine. This also results in the manufacture of alkoxyl and epoxy alkyl radicals. One potential by-product or release product from the immune macrophages when engulfing the pigment lutein is aldehyde which inactivates Cytochrome P-450. ?Genes encoding several serum complement components and the gene(s) for steroid 21-hydroxylase (21-OH) have been located in the class III region of the major histocompatibility complex (MHC). All these genes are highly polymorphic in man, and these polymorphisms have been used to draw conclusions about the structure and function of these genes. For example, electrophoretic polymorphisms of the fourth component of complement (C4) have been shown to be controlled by two closely linked genes, which also control expression of the red cell antigens. (Rodgers and Chido) Steroid 21-OH deficiency (D) can occur in several forms which differ in severity, and because of genetic linkage disequilibrium with different HLA antigens the inheritance of these forms is consistent with the existence of several alleles at a single locus. When severe 21-OH D occurs in association with the HLA haplotype A3;Bw47;DR7, there is a simultaneous null allele at one of the C4 loci. This was hypothesized to result from a single deletion or rearrangement affecting the 21-OH and C4 loci and perhaps the HLA-B gene as well. These experiments showed that at least one structural gene for the cytochrome P450 specific for 21-hydroxylation is located in the MHC, probably very near the C4 genes, and a mutation in this gene results in 21-OH D. Cosmid clones have been used to locate the 21-OH genes both in man and mouse. In both species, there are two 21-OH genes, each located immediately 3' of one of the two C4 genes, and oriented in the same direction as the C4 genes. In man, the gene located 3' of the C4B gene is deleted in 21-OH D on the Bw47 haplotype, but the gene 3' of the C4A gene is deleted in hormonally normal individuals on the A1;B8;C4AQO;C4B1;DR3 haplotype. Thus the 21-OH B gene is normally active in man, but the 21-OH A gene is not.? 41 4p Defects of chromosome 4p include: Hermansky-Pudlak syndrome (HPS). Wolf-Hirschhorn syndrome: Clinical features include mental retardation, seizures, distinct facial appearance, and midline closure defects. 4 Parkinsonism. 5p Melanin-concentrating hormone (MCH) gene (Viale A et al). Defects of chromosome 5p include: Primary ciliary dyskinesia, left-right asymmetry (Olbrich H et al). ?The spectrum of heterotopic calcification or ossification is expanding because of the reports of several kindreds with calcium pyrophosphate deposition disease, apatite deposition disease, and others with less common syndromes associated with extracellular matrix calcification, such as fibrodysplasia ossificans progressiva and related syndromes.? 3 Although calcification problems have been identified to coexist with autism i.e. tuberous sclerosis and PKU, the genetic findings would indicate a probable predisposition to arthritic conditions, and yet these have not been reported in the literature. Potentially the immune system involvement in purine and pyrimidine disturbances includes removal of formed crystals via the skin rather than deposition, possibly to protect the kidneys. The findings of an association of chromosomes 5p (calcification) and 7q (hemochromatosis) in autism research (7q in multiple genome studies) would tend to support the findings of a pilot study ?Preliminary study of altered skin temperature at body sites associated with self-injurious behavior in adults who have developmental disabilities,? J. Symons, A. Sutton, and W. Bodfish, American Journal on Mental Retardation, Vol. 106, No.4, 2001. The article includes ?skin temperature changes can be indicative of neuropathy . . . For each participant the body site targeted most frequently for self-injury may itself change skin temperature, evidence from other animal studies suggests that neuropathy can lead to self-injury. For Instance, they note, self-mutilation is a common finding in animals with dysesthesia, or abnormal sensations caused by lesions of the sensory nerve pathways. In addition, cases of intellectually normal individuals who targeted self-injury toward areas with neuropathy and altered skin temperature have been documented. ?The researchers suggest that self-injury may provide temporary relief of neuropathy-caused pain or discomfort (as when a child scratches at a scab or chicken pox lesion), but may lead in the long term to more irritation that in turn generates more self-injury. We suggest that, in autism, the pain and discomfort is caused not by sensory neuropathy but by the immune system removal of calcium and other crystals as well as other breakdown products of lutein (formic acid, epoxy residues) through the skin. ?The researchers note that all four of their subjects responded well to naltrexone, a substance that blocks opioid receptors and alters perception of pain. They suggest that further studies examine whether naltrexone treatment, although it has no known effect on neuropathy itself, is more effective in individuals with skin temperature differences at self-injury sites. ?In addition, Symonds and colleagues say, ?one clinical implication of a pain related model of self-injurious behavior (SIB) is that treatments for peripheral neuropathies may provide an effective treatment option for some subset of SIB cases.? They note that several studies show decreased self-injury during treatment with transcutaneous electrical nerve stimulation (TENS), a treatment that blocks peripheral pain signals.?? 45 Symptom versus behavior In real terms, the combination of these processes - genetic, immune and environmental: genetic predisposition, immune reaction and environmental stimuli - result in the signs and symptoms which in autism are called behaviors. Current research is beginning to provide insights into what the autist is experiencing from his or her own biochemistry, physiology and environment. We are beginning to understand that the world of the autist is a little different and their perception of the world is also quite different. Since I have this lutein reaction in my own body, and have spoken to many autists who have related their experiences to me, I feel that it is worthwhile to contribute some information on how these scientific terms relate to real life experiences. Vision Unlike some autists who are blind and others who are born blind and then have visual maturation with the onset of autistic ?symptomology? I was born blind in one eye. I did not obtain vision in my left eye until my second pregnancy and the ophthalmologist suggested that increased steroid hormones produced during pregnancy probably resulted in the ?visual maturation? at the age of 21. To this I ask why are steroid hormones not considered for this type of childhood visual disturbance? The eye doctors had no trouble putting me through wearing a patch over my sighted eye which resulted in extreme anxiety and then stating there was nothing else he could do. The vision I acquired in my left eye was partial, the depth perception was quite different from my right eye. This also caused anxiety and so I had to wear glasses. Since my right eye had exceptionally good vision I did not see as well with glasses even though the right eye lens was clear glass. So, I got a contact lens for my left eye. This was somewhat helpful except when I took the contact lens out I got a headache. Eventually I got an eye infection and steroid drops resulted in better depth perception and I could go without glasses. With both eyes open the visual images were from my right eye only. It was only when I closed my right eye that I could see blurry images with my left eye. When I began the lutein free diet at the age of 35 my vision changed within a year. I could see from my left eye clearly for the first time and this was a strange experience. First I felt like I was very tall looking way down to the ground. The next moment I might feel very short as if I had shrunk to a midgets height. It took several days for these visual distortions to stop. I met Dr. Gwen , trained as an Irlen Lens diagnostician and also a psychologist in Atlanta. Dr. was testing , my adopted autistic (declassified) 15 year old daughter for Irlen lenses. I also had a screening and so did my husband. My Irlen lenses are a combination of pink and blue for the left eye and plain blue for the right eye. I haven?t gone outside without the Irlen lenses since I got them 4 years ago. As I read about autism and studied the individuals with autism and began to write about autism it was frustrating to see how impersonal words would seem when trying to describe autism. To say my vision is not bilaterally synchronized doesn?t tell you how visual stimuli coming in at different speeds from different sides affects me in real life. It affects me as I react differently to someone or something approaching me from the left side or the right side. It means I consider this subconsciously when I choose my seating in a restaurant or at a meeting. It means that when I am riding in a car the way the traffic moves on one side with the passing scenery still on the other side results in spontaneous panic reactions, hand-flapping and rigid finger movements. I suspect that my visual perception is similar to some of the autistic population and for others there are more severe complications and for some less. I take cod-liver oil to support my vision even though I do not maintain a dairy free diet. I find it difficult to take in enough butter, fresh cheeses, liver and fish to meet the RDI for vitamin A. It would be nearly impossible for those on a dairy free diet. Not directly related to vision but still related to the eye area are the hair follicles of the eye lashes. Some of these, about 5 or 6, on my right upper eye lid have follicles that fill with fluid cyclically. The fluid can become hardened and the eyelash becomes painful. It feels like a needle sticking into the area. So, I remove these eye-lashes and experience immediate relief from the pain. So, the psychologists can call it trichotillomania (known to co-occur with autism) if they want to but I call it a rational reaction to pain. So, now I am quite satisfied that my vision is as good as it can be with the Irlen lenses. Before starting the diet, my vision was strongly affected by a lutein (food) reaction. I lost depth perception altogether and would have to hold my hand against the wall to move towards a chair or bed where I remained until the worst of the symptoms passed (distorted vision, loss of depth perception, auditory processing difficulties, vice-grip type headache, profuse sweating, nausea, burping followed by muscle contractions, vomiting, diarrhea and urinary incontinence). Since I didn?t know what lutein was or which foods contained lutein I didn?t know when this was going to happen. In early childhood (infancy to age 5) I had a very limited self-selective diet: tomato soup, potato chips and baby rice cereal and I would drink coke, sprite and coconut milk. Naturally lutein free, very limited dairy and not much wheat. Parental intervention or rather forced feeding led to severe reactions but also resulted in my finding more foods that I could tolerate: White bread as toast with butter, chocolate chips (dark chocolate), whipped cream, cream cheese, most meats and lettuce were safe foods. Foods that made me ill were discovered one by one: green peas, egg yolk, spinach and strawberries. These foods didn?t appear to have anything in common. They were not in the same food group or the same food family. I studied the food groups, the nutrition manuals, the chemistry books and still there was nothing until I read ?The development and application of a carotenoid database for fruits, vegetables, and multicomponent foods? by Jaspreet et al, published in the Journal of The American Dietetic Association, March 1993 (Vol.93). All these foods contained lutein and more foods not listed in the fruits and vegetables article also contained lutein (i.e. chicken fat). I was now armed with information and I produced a lutein free, nutrient balanced diet right down to the individual amino acid levels for daily intake. I noted what foods had to be in the diet and what nutrients would have to be supplemented if the menu was not adequate. I put my diet into action and have been well with a few mishaps ever since. As I studied how an immune response of this type might work in the human body I was convinced that this same approach might help my autistic foster daughter. As soon as the legal process of adoption was complete I placed her, with her pediatricians permission, on the lutein free diet. Sara blossomed at age 11, began speaking in sentences, stopped toe-walking and lost 17 of the 18 characteristics of autism which she had expressed until we implemented the diet change. Thus the ?Sara?s diet? story began. One of the teenage autistic females who implemented the lutein free diet later described how her eyes felt when she was having a food reaction, she said ?It felt like my eyes were melting?. Hearing According to standard testing measures my hearing is good. I can play a musical instrument and not get thrown out of a church choir. I have tinitus (vibratory), ?ringing in the ears? but to me the sound is best described as the sound that crickets make, lots of crickets. I like the sound. At times I have managed to restrict my diet enough that the sound goes away completely but then I feel vulnerable as normal everyday sounds become loud and painful. I can imagine that for some people who develop tinitus they must experience the continual sound as painful and annoying, maybe even unbearable at times. A long time ago people who were diagnosed with Meniere?s disease ( a type of deafness) were prescribed a carotenoids free diet. This was before World Health Organization determined that carotenoids were good for everyone (they didn?t do the research and they were wrong, the research has since been done but no change in WHO policy has occurred). Would the World Health Organization admit such an error and make a retraction jeopardizing modern practices of putting more carotenoids into our diet, adding beta-carotene to rice, increasing the lutein production in potato and cucumber and supporting the development of edible vaccines in carotenoids bases. I don?t think they will. Nor does anyone expect them or science in general to acknowledge the vaccine contribution to modern day disease. But the promotions of the World Health Organization have impacted my life tremendously. I tried to take into account their recommendations and I suffered. Every time I ate a lutein containing food I became ill. One of the symptoms was loss of auditory perception. People?s mouths would be moving but I could not hear any sounds. The tinitus would intensify and block out all incoming sound. Fortunately this was temporary and when the headache went away my hearing returned. I suspect that I like the tinitus because it helps me to tune out the world. I can study and concentrate on my work better with the continual hum. Sometimes a sound from the outside world penetrates and the vibration from the sound is disturbing. By disturbing I mean that my body panics and I cannot tolerate the noise, I become unwell, nauseated and fearful. The sound of a paint compressor is one type of sound which can produce this panic reaction. I will leave the area of the sound and return when the sound is gone. Smell Some smells result in immune reactions, particularly anything with pine oil (Christmas trees and cleaning products), some commercial carpet shampoo, brass cleaner, finger nail polish, some perfumes, deodorants, hair sprays, oil based paints. Often these are epoxy odors or substances that contain pinene. The reaction to fumes is quite different, usually intoxicating, euphoric even. Lengthy exposure can be more intense resulting in crying for no apparent reason or hysterical laughter. I have discovered that I am especially allergic to the smell from pitocin. When the women on the labor ward were put on pitocin IV?s I could not enter the ward and had to work in a different area of the hospital, the reaction was respiratory, asthma-like (coughing, wheezing, shortness of breath) and I do not have asthma. The smell of fresh oranges being peeled results in an intoxicating ?high?. Taste I am not aware of any issues with taste. I like the taste of most foods but I do have sensory issues. Metal, such as forks and spoons cannot touch my teeth. Only certain teeth actually touch the food. Getting me to chew took some effort on my parents part. But I have many autistic friends and one of them says ?Getting an autistic person to eat something they don?t like is like trying to get a normal person to eat a hairball?. Touch I guess I spent a lot of time examining my own skin, often with a microscope. I was curious as to why I had blue ink like deposits in the pores of my developing breasts, why I had hard white crystal-like substances erupting from the pores on my upper arms, and what made blue ear wax. Some people spent their teen years socializing and I spent mine in the medical library. The textures which bother me the most are cardboard, the cotton wool filler that comes inside medicine bottles and some fabrics, particularly wool. I won?t wear anything that is uncomfortable (too binding). Physical touch is good but I am easily startled by unexpected touch. My skin is good now with only occasional itching when I get too much calcium in the diet or too much oxalates. I have experienced a lot of phenomena with substances that are excreted through my skin, small round white lumps which pop out and look like small pearls. These don?t pop out easily and yet until they are out they are painful, they feel like daggers under the skin. Usually the lumps are smaller like a large grain of salt. Sometimes they are just the hair follicle wax which has hardened and crystallized. A food reaction would result in itching and burning which felt like being bitten all over by mosquitoes with no visible rash. Sara?s reactions in the skin were quite different. Often she would have 3 to 7 blisters which looked like infected mosquito bites on her skin ? small clear to yellow blisters which she scratched as soon as she could get to them. Since being on the diet these no longer appear. I believe these are substances released from the macrophages which are derived from plant foods (triterpenoids, epoxides) which are agglutinated and removed (in the autist) via the skin. I have seen many pictures of autists with these ?prurigo? type eruptions. My reaction to some types of pain is abnormal. I have experienced a rush from head to toe resulting in euphoric type feelings from grease burns and a broken foot. I had no pain when I had an appendicitis or after the surgery. Other types of pain, particularly ovulation and toothache are overwhelming at times. Balance My balance is generally good but I did practice walking with a book on my head (grandmother?s suggestion). I was not good at sports, possibly because of the visual problems but I was very good at deck tennis (catching a rubber ring that came flying over a net). As far as sports went I wasn?t the last one chosen, I wasn?t even an option. I was designated as the instructors helper. I have experienced vertigo, severe and disabling when it happens. It can be triggered by kaweol, an oil in arabica coffee or from too much xanthine (coffee, tea, chocolate or violaxanthine in purple vegetables). Violaxanthine can be converted to zeaxanthine in the body, which may be needed to protect the eyes, and works similar to lutein in the eyes. The lutein containing foods are also generally zeaxanthine foods, so getting the violaxanthine foods into the diet is important, if tolerated, to provide another source of protection for the eyes. Lycopene is another food that can be converted to photoprotective pigments in the body. Once lutein has been out of the diet for 4 months, lycopene foods (e.g. tomatoes) can usually be safely returned to the diet. Once the autist is accommodated with the lutein free diet and he or she no longer has the strong food related anxiety then it becomes easier to get the non-lutein fruits and vegetables into their diet. Well-being As the term autism was first used to describe ?withdrawal from the fabric of social life? it is easy to understand that people who are not well withdraw from the fabric of social life. People who are not well do not experience a sense of well-being and this is necessary to move towards developing emotional maturity. People with autism, a movement disorder suffer with symptoms which can be seen and heard as well as hidden from view; dyskinesia: burping, jerking in the night, hiccups, muscle contractions. These symptoms can and do interfere with sleep and a sense of well being impeding our ability to develop skills. The skills of emotional maturity are necessary for the development of social skills. So, to move forward with an autistic individual one must look at the world through their eyes, hear the world differently, look at foods differently. The environment has to meet their needs. The tools must be modified and adapted to meet their needs. Habilitating a generation of autists is not going to be easy. It will take people with foresight, insight and fortitude. Most of the autistic population will have strength and determination (it takes a lot of determination to limit one?s own diet to the minimal foods many of these individuals accept). We have to help them learn to use their strengths rather than holding them back through their weaknesses. Just because some won?t be able to speak doesn?t justify not teaching them to read. Just because many write in large scrawling letters doesn?t mean they can?t learn to write on a keyboard. The consistency of the findings in autism: relationship to pigment metabolism, immune and genetic findings, consistent markers i.e. transferase deficiencies, elevated GFAP, urinary metabolites i.e. elevated neopterin, biopterin, IAG and serum serotonin levels strongly suggest that symptoms which occur with consistent biochemical, immune and IoGc markers would indicate a common causal factor. Desorgher BSc, BSC, MA-TFM, NR, NM http\\:www.saras-autism-diet.freeservers.com/ Quote Link to comment Share on other sites More sharing options...
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