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Biokjemisk Ubalanse Og Biomedisinsk Behandling Av Autisme: Gjennomgang Av Litteraturen

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Biokjemisk Ubalanse Og Biomedisinsk Behandling Av Autisme: Gjennomgang Av Litteraturen Biokjemisk ubalanse og biomedisinsk behandling av autisme: Gjennomgang av litteraturen. Mars 2010 © Utarbeidet av: Hanne Bjørg Walker1 Kathrine Ebbesen Rør1 Dr. med. Karl Ludvig Reichelt, Ph.D2 Professor Eremitus Tore Midtvedt, Ph.D3 Susan Owens, MAIS4 Lege Geir Flatabø5 Professor Svein Eikeseth, Ph.D6 Bidragsytere: Dr. Jeff Bradstreet, MD, MD(H) FAAFP 7 Dr. Elisabeth Mumper, MD8 Førsteamanuensis Bjørn Bolann, Ph.D9 1 Vår Vei, Parent network for children with autism, Norway 2 Pediatric Research Institute, Rikshospitalet University State Hospital, Oslo, Norway 3 Karolinska Institute, Stockholm, Sverige 4 Autism Research Center, San Diego, CA, USA 5 Medisinsk Helsesenter, Ulvik, Norge 6 Akershus University College, Lillestrøm, Norge 7 International Child Developmental Research Centre, Florida, USA 8 The Rimland Centre, USA 9 Institutt for indremedisin, Seksjon for medisinsk biokjemi, Haukeland Universitetssykehus, Bergen, Norway Oppsummering & konklusjoner Mandatet Mandatet er gitt av Helsedirektoratet i brev av 14. november 2006: Beskrive aktuelle biokjemiske ubalanser og biomedisinsk behandling for barn med autisme. Autisme Autisme – Autism Specter Disorder(ASD) er et komplekst klinisk problem for alle som arbeider med mulige årsaksforhold og for alle som søker etter effektive behandlingsmetoder. Det tradisjonelle synspunktet som mange fagpersoner har er at autisme er en genetisk hjerneforstyrrelse som ikke kan behandles. Antall barn med ASD øker. Forekomst av en ren genetisk betinget sykdom kan bare vokse i takt med popula- sjonsøkning. Selv om det er sannsynlig at gener spiller en rolle ved ASD, kan ikke økningen forklares ut fra end- ringer i gener eller i diagnosekriterier, men gjør det overveiende sannsynlig at andre faktorer også spiller en rolle. I denne kunnskapsoppsummeringen vises til mange mulige faktorer. Det kan ikke understrekes sterkt nok at på- gående forskning stadig avdekker funn som kan bli verdifulle i fremtidig diagnostikk, terapi og prognose. Kunnskapsoppsummeringen bør ikke sees på som statisk og den endelige sannhet, men som en sammen- stilling av faktorer som man må ha i mente når man utformer den videre veien som skal gås i behandlingen av barn med autisme. Det nye synet om at autisme ikke er en hjerneforstyrrelse, men en forstyrrelse som påvirker hjernen kan beskrives som følger. Autisme er en multiorgan sykdom som innvolverer immunologiske og metabolske dysfunksjoner som kan bli forverret av miljøfaktorer i genetisk sårbare individer – såkalte subpopulasjoner. Kunnskapsoppsummeringen trekker frem noen viktige immunologiske og metabolske faktorer og beskriver noen miljøfaktorer som kan være av viktighet for diagnosen. Blant disse miljøfaktorene inkluderes også dietære faktorer som gluten,kasein osv. Det er økende antall publiserte rapporter som beskriver markert bedring/ endring av autistiske symptomer i undergrupper av barn hvor slike faktorer er eliminert. Det sier seg selv at hver suksessfull historie representerer en fantastisk lettelse for familieliv samtidig som det har en substansiell økonomisk verdi for samfunnet. Det er en diagnostisk utfordring å finne de forskjellige triggerne og undergruppene. Basert på det vel etablerte, men fremdeles utfordrende paradigme skift at “autism kan behandles”, så for- tjener hvert eneste barn fortjener å bli utredet og behandlet på optimal måte. Forord Autisme kan beskrives som en atferdsforstyrrelse med underliggende biologiske faktorer, influert av gener og av interaksjon mellom gener og miljø. Det er holdepunkter for at de underliggende biologiske faktorer er av en omfattende størrelse. For å kunne påvirke tilstanden er det nødvendig med en god forståelse av mange typer ulike reaksjonsveier. Ny viten slår fast at man i stedet for å se autisme som en hjernebasert skade, må ses på som en funksjonsforstyr- relse som påvirker hjernen (Herbert 2005).1 Det er mer enn et halvt århundre siden det ble tydelig demonstrert at forekomsten av en bestemt tarmflora økte sensitiviteten i vev til flere forskjellige nevrotransmittere (Strandberg et al. 19662, Gustafsson et al. 1970).3 Dette endrede synet på autisme fra “sterkt genetisk betinget” til “genetisk påvirket”, gir rom for epigenetikk, sto- kastiske effekter, pleiotropisme, epistase, variabel ekspressivitet og interaksjoner mellom gener og miljø (Veen- stra-Vanderweele et al. 2004)4, (Herbert 2005).1 Innhold Oppsummering & konklusjoner................................................................................................................... 2 Forord............................................................................................................................................................... 3 1. Innledning .................................................................................................................................................. 6 2. Mandat......................................................................................................................................................... 7 2.1. Bakgrunn..........................................................................................................................................................7 2.2. Formål...............................................................................................................................................................7 2.3. Prosjektgruppe................................................................................................................................................7 2.4. Søkestrategi......................................................................................................................................................7 2.5. Inklusjonskriterier..........................................................................................................................................7 2.6. Innsamling og analyse av data......................................................................................................................7 2.7. Prevalens...........................................................................................................................................................7 2.8. Miljøfaktorer....................................................................................................................................................8 3. Biokjemiske og immunologiske faktorer................................................................................................ 8 3.1. Nevrologi og immunologi.............................................................................................................................8 3.2. Th1/Th2............................................................................................................................................................9 3.3. Autoimmunitet............................................................................................................................................. 10 3.4. Cytokiner i hjerne og tarm; NK-celler..................................................................................................... 12 3.5. Mage tarm..................................................................................................................................................... 13 3.6. Mikrobiell metabolisme i mage–tarm..................................................................................................... 18 3.6.1. Neurotoxin..............................................................................................................................................................................19 3.6.2. Endotoksin..............................................................................................................................................................................20 3.6.3. Bakterielle korte frie fettsyre.............................................................................................................................................20 3.6.4. Svovelmetabolisme. ............................................................................................................................................................20 3.7. Oksalat........................................................................................................................................................... 20 3.8. Oksidativt stress........................................................................................................................................... 22 3.9. Virus infeksjoner.......................................................................................................................................... 24 4. Miljøstudier..............................................................................................................................................25 4.1. Miljøgifter...................................................................................................................................................... 25 5. Biomarkører..............................................................................................................................................30 5.1. Blodbilde........................................................................................................................................................ 31 5.1.1. Røde og hvite blodplater med differensiealtelling.....................................................................................................31 5.1.2. Metabolsk panel...................................................................................................................................................................31
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