Parent and Professionals Talk -UH Medical Education Center 4.25.15

!  I!have!consulted!for!Nutricia!and!Nestle!
!  Research!and!support!funding!has!come!from!
!
!
!
!
!
Timothy!Buie!MD!
Massachusetts!General!Hospital!for!Children/!
Harvard!Medical!School!
The!Newman!Foundation!(Newman’s!Own),!
AutismSpeaks,!The!Autism!Research!
Institute,!Nutricia,!The!American!Academy!of!
Pediatrics,!The!Simons!Foundation!
!  I!have!no!conflicts!to!disclose!regarding!the!
information!offered!in!this!presentation!!
© PediGI, LLC !
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
!  Discuss!differences!in!children!with!autism!that!
might!be!relevant!to!medical!coNmorbidity!
!  Review!medical!literature!regarding!GI!issues!in!
autism!
!  Explore!one!diagnosis!(GERD)!in!autism!as!an!
!  Discuss!major!treatment!considerations!in!a!
general!sense!
!  Be!available!for!specific!questions!after!our!
session!
!  Please!hold!questions!during!the!talk!and!we’ll!
do!our!best!to!cover!things!
example!
!  Consider!coNmorbidity!and!the!hypotheses!
focused!on!possible!GI!contribution!to!autism!!
!  Qualitative!impairment!in!social!interaction!
!  Qualitative!impairments!in!communication!
!  Restrictive,!repetitive!and!stereotyped!
patterns!of!behavior,!interests!and!activity!
Must!meet!criteria!A,!B,!C,!and!D:!
A.!Persistent!deficits!in!social!communication!and!
social!interaction!across!contexts,!not!accounted!for!
by!general!developmental!delays!
B.!Restricted,!repetitive!patterns!of!behavior,!
interests,!or!activities!!
C.!Symptoms!must!be!present!in!early!childhood!(but!
may!not!become!fully!manifest!until!social!demands!
exceed!limited!capacities)!
D.!Symptoms!together!limit!and!impair!everyday!
functioning!
!  A!well!defined!profile!of!coNmorbidities!
!  An!inclusion!of!sensory!processing!disorders!
or!the!impact!of!these!issues!when!present!
!  A!delineation!of!when!behaviors!seen!in!ASD!
may!cross!into!additional!diagnoses!such!as!
OCD,!ADHD,!eating!disorder!etc!
!  Guidance)about)what)conditions)seen)in)
autism)should)not)be)accepted)as)autism)
)))
!
CDC!March!2014:!!
!  CoNmorbidity!is!commonly!discussed!
regarding:!!
!  1/68!Children!have!ASD!
!  !1/42!Boys!have!ASD!
!  !1/189!Girls!have!ASD!
!  1/6!Children!in!the!US!has!a!
!  1)!Genetic!syndromes!
!  2)!Associated!psychopathology!
!  3)!Medical!Conditions!
▪  A)!Epilepsy!
▪  B)!Gastrointestinal!Disorders!
▪  C)!Food!Allergy,!Immune!Dysregulation!
▪  D)!Catatonia!
developmental!disability!
Prevalence)of)Autism)Spectrum)Disorder)Among)Children)Aged)8)Years)—)Autism)and)
Developmental)Disabilities)Monitoring)Network,)11)Sites,)United)States,)2010)
!!!!!!!!Surveillance!Summaries!March)28,)2014)/)63(SS02);1N21!
!
!
!!
!
Earlier!studies!may!have!had!an!acquisition!
limitations!(for!this!talk!Autism=ASD):!
!  Taylor!(2002)!reports!chronic!GI!complaints!in!
17%!of!children!with!autism!evaluated!
!
!  Fombonne!2001!cites!GI!complaints!in!an!
autism!cohort!at!18.8%!!
!
!  Malloy!(2003)!reports!24%!of!children!with!
ASD!have!chronic!GI!issues!
!
!
!  ValicentiNMcDermott,!2006,!evaluated!children!
with!ASD!and!control!groups!matched!for!age,!
sex!and!ethnicity!(50!children/group)!
!  70%!of!children!with!ASD!had!GI!Issues!
compared!to!
!  42%!of!children!with!developmental!disorder!
other!than!ASD!
!  28%!of!children!with!typical!development!!!
Horvath!identified!at!least!one!GI!complaint!in!84%!
of!children!with!ASD!compared!with!31%!of!
unaffected!sibling!!(2002)!
!  Vanderbilt/MGH!review!of!the!AGRE!database!
found!GI!issues!in!ASD!in!43%!in!ASD!vs.!4%!
unaffected!siblings!(2009)!
!  Schrieber!and!Minshew!report!61%!of!children!with!
ASD!had!GI!symptoms!and!associated!features!of!
affective!and!behavioral!symptoms!(2012)!
!  GI!issues!in!autism!are!common!and!parental!
concerns!correlate)well)with!physician!assessment!
(Gorrindo!2012)!
! 
What!might!GI!symptoms!look!like!in!
an!individual!with!autism?!
!
!  After!seeing!the!videos!of!these!children,!I!hope!
you!can!understand!my!personal!concern!that!
we!are!not!able!to!properly!define!a!prevalence!
for!underlying!medical!issues!(including!GI)!
using!our!usual!methods!
!  Behaviors!in!autism!come!for!many!reasons,!not!
all!have!a!function!that!may!be!related!to!autism!
itself!(frustration!with!transition!or!inability!to!
communicate!alone)!
!  No!one!wants!to!self!injure!
!
!
! 
Others!have!built!on!the!suggestion!that!many!children!
with!autism!suffering!GI!symptoms!have!a!variety!of!GI!
findings!including:!!
!  1)!Inflammation!(Horvath!1999)!
!  2)!Increased!intestinal!permeability!(D!Euphemia!1996)!
!  3)!Impaired!digestion!of!carbohydrates!(Horvath,!
Kushak,!Williams)!
!  4)!Disruption!of!typical!microbiota!(Feingold,!Williams,!
Kang)!!
!  5)!Altered!immune!response!to!inflammation!(Ashwood)!!
!  Early!Dietary!or!GI!Discussions!in!Autism!were!
hypotheses!of!causation:!
!  Opioid)Peptide)Theory):!Shattock!(1990)!and!
Reichelt!(1991)!peptides!from!milk!and!gluten!
caused!!childhood!schizophrenia!(autism)!
!  Autistic)Enterocolitis:!Wakefield!(1998,!2000)!
intestinal!permeability!induced!by!intestinal!
infection!with!Measles!virus!caused!immune!
disruption!and!opioid!peptides!could!be!more!
able!to!set!off!condition!!!!!
!  MultiNfactorial!issues!well!described:!!
!  1)!Selectivity!may!well!be!a!core!to!autism!as!part!!
of!perseverative!behavior!
!  2)!Textural!sensitivity!could!be!related!but!often!
occurs!associated!with!GE!Reflux!and!can!be!seen!
with!oral!allergy!response.!
!
!  Reviews!are!inconsistent!but!include!concern!
for!inadequate!Calcium,!Choline,!and!Vitamin!
D.!!
!!!!In!individual!cases,!selectivity!can!set!up!for!
isolated!deficiencies!(such!as!2!cases!of!
scurvy!we!have!identified)!but!the!large!scale!
studies!show!surprisingly!adequate!nutrient!
intake!for!most!children!despite!restrictive!
eating!patterns!!
! 
Elder!et!al*!2006!doubleNblind!crossover!trial!
CaseinNfree,!GlutenNfree!diet!in!15!autistic!children!
showed!no!benefit!of!diet!in!a!12Nweek!study!
! 
Blinded!parents!reported!benefits!not!identified!by!
testing.!Perhaps!subtle!changes/benefits!will!not!be!
retrieved!through!standard!tests.!
!
! 
Similar!trial!from!Susan!Hyman’s!group!in!Rochester!
reported!in!abstract!form!showed!no!benefit!from!
CF,!GF!diet.!
!  Food!allergy!was!reported!in!36%!of!36!children!
with!autism!!(Lucarelli!1995)!!
!  Families!report!their!children!with!ASD!had!a!food!
allergy!or!sensitivity!in!over!40%!(Horvath!2002)!
!  Higher!frequency!of!IgE!mediated!food!allergy!in!
children!with!ASD!compared!to!unaffected!siblings!
(Trajkovski!2008)!
!  Sensitivity!may!=!allergy,!“drugNlike”!effect!of!food,!
maldigestion!!
! 
Knivsberg,!1990:!Selected!patients!with!high!gluten!
opioid!peptides!in!urine.!8/10!were!reported!to!have!
behavioral!improvements!noted.!Duplicated!study!
in!2002!
! 
Sponheim!1991:!Selected!4!autistics!for!glutenNfree!
diet,!behavior!worsened!
! 
Whiteley,!1999:!Observation!study!of!gluten!free!
diet,!2/3!had!behavioral!improvements!noted!
! 
Where!else?!Unraveling,the,Mystery,of,Autism,,by!
Karen!Seroussi!(Simon!and!Schuster,!N.Y.N.Y.!2000)!
*J!Autism!Dev!Disord.!2006!Apr;36(3):413N20!!
!
!  Risperidone!7o%!of!patients!with!autism!and!
irritability!showed!reduction!in!irritability,!
repetitive!speech!and!SIB.!No!effect!on!core!
autism!symptoms!
!  ABA!or!TEACCH!educational!models!are!
validated!as!successful!models!for!progress!but!
resolution!of!autism?!Not!usually!
!  Does!a!diet!have!to!resolve!autism?!
!  MGH!has!just!concluded!a!CFNGF!diet!study,!
sponsored!by!Nutricia,!evaluating!the!
hypothesis!that!there!are!more!likely!
candidates!for!success!with!dietary!restriction!
!  Enrollment!is!based!on!gastrointestinal!
symptoms!for!inclusion!?!Better!candidate!
pool!
!  A!remarkable!allergy!workNup!is!part!of!this!
study,!elemental!diet!support!is!offered!
during!the!restriction!period!!
!
I’ll!let!you!know!what!we!find!soon!
!
!  Children!ages!3!N!9!years!old:!24%!(History!of!
!  Consider!one!coNmorbidity:!GERD!
symptoms!consistent!with!GERD)!
!  Children!ages!10!N!17!years!old:!8%N25%!
(Experienced!GERD!symptoms!by!child!or!
parental!report)!
!  Children!with!autism!have!the!right!to!usual!
medical!conditions!and!to!our!knowledge!
autism!does!not!protect!us!from!other!medical!
issues!or!reduce!prevalence!
Hoarseness
!  Joanna!has!Sandifer’s!syndrome!with!posturing!
Dental erosions
from!reflux!causing!pain!
Otitis / sinusitis
Extra-esophageal
manifestations of
GERD
Chronic sore
throat
Chronic cough
Wheezing /
asthma
Apnea /
bradycardia
El-Serag H et al. Gastroenterology 2001;121:1294-9
Tasker A et al. Laryngoscope 2002;112:1930-4
!  Russell!(1989)!reported!2!patients!with!SIB!
unresponsive!to!psychoNpharmacological!
intervention!!who!had!resolution!on!antiN
emetics!
!  These!agents!were!neuroleptic!drugs!so!
improvement!may!not!be!related!to!reflux!
management!
!  Horvath!(1999)!evaluated!36!patients!with!
chronic)diarrhea)by!endoscopy.!69%)had!
Grade!1N2!esophagitis!!histologically!
!  Histories!did!not!identify!if!the!finding!of!
esophagitis!or!UGI!inflammation!had!a!clinical!
correlate!
!!!
Adams et al. BMC Gastroenterology 2011, 11:22
!  Key)Statement)(Statement)1):!Individuals!
with!ASDs!who!present!with!GI!symptoms!
warrant)a)thorough)evaluation,!as!would!be!
undertaken!in!individuals!without!ASDs!who!
have!the!same!symptoms!or!signs.!!!!
! 
Statement)2:!GI!conditions!reported!to!be!
common!in!individuals!without!ASDs!are!also!
encountered!in!individuals!with!ASDs.!
! 
Statement)3:!The!prevalence!of!GI!
abnormalities!in!ASDs!is!incompletely!
understood.!!
! 
Statement)4:!The!existence!of!a!GI!disturbance!
specific!to!persons!with!ASDs!(e.g.,!“autistic!
enterocolitis”)!has!not!been!established.!
Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in
Individuals With ASDs: A Consensus Report
T. Buie et al, Pediatrics 2010; 125: S1-S18
Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in
Individuals With ASDs: A Consensus Report
T. Buie et al, Pediatrics 2010; 125: S1-S18
! 
Statement)6:)Individuals!with!ASDs!and!GI!
symptoms!are!at!risk!for!problem)behaviors.!!When!
patients!with!GI!disorders!present!with!behavioral!
manifestations,!the!diagnostic!evaluation!can!be!
complex.!
! 
Statement)8:)Education!of!caregivers!and!health!
care!providers!is!necessary!to!impart!knowledge!of!
how!to!recognize!typical!and!atypical!signs!and!
symptoms!of!GI!disorders!in!individuals!with!ASDs.!
! 
Discussion!of!presentation!of!several!common!GI!
problems!in!children!with!autism!including!
abdominal!pain,!constipation,!diarrhea!and!gastroN
esophageal!reflux!
! 
Some!basic!suggestions!for!evaluation!and!
treatment!are!offered!holding!mostly!to!established!
guidelines!for!pediatric!patients!in!general,!until!
better!data!is!available!to!guide!evaluation!and!
treatment!!
Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With
ASDs: A Consensus Report T. Buie et al, Pediatrics 2010; 125: S1-S18
Recommendations for Evaluation and Treatment of Common Gastrointestinal Problems
in Children With ASDs
T Buie et al, Pediatrics 2010; 125: S19-S29
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S19
Could!GI!issues!CAUSE!autism?!
!  Environmental/nutritional/microbiome!
associated!factors!modulating!genetically!
predisposed!individuals!
!!
!  An!inflammation!model!where!some!body!
process!(colitis,!allergy,!infection)!releases!
chemical!or!immune!mediators!that!affect!
brain!function!(Vargas!2005,!Welch!2005)!
!  Bacterial!flora!disruptions!may!alter!behavior!
!  Bacterial!flora!disruptions!exist!in!the!autism!
population!
!  There!are!a!number!of!pathways!potentially!
accounting!for!altered!pain!sensitivity,!
emotional!stability!!by!altering!microflora!
!  Diet!may!alter!microflora!and!metabolome!!
!  Animal!models!have!been!developed!to!
induce!an!autismNlike!change!(MIA!mouse)!
!  Can!we!compare!mouse!behavior!to!the!
human!condition!of!autism?!
!  Are!the!mice!evaluated!representative!of!a!
phenotype!seen!in!children!with!autism?!
(Children!born!from!autoNimmune!maternal!
state,!children!at!risk!for!intestinal!
permeability!abnormalities)!
Cell 2013
!  In!AUTNGI!subjects,!ileal!transcripts!for!the!
disaccharidases!sucrase!isomaltase,!maltase!
glucoamylase,!and!lactase,!and!the!
monosaccharide!transporters,!sodiumN
dependent!glucose!coNtransporter,!and!
glucose!transporter!2!were!significantly!
decreased.!(Williams!et!al,!PLOS!One!Sept!
2010)!
!  This!study!supports!our!previous!enzymatic!
findings!of!disaccharide!deficiency!and!goes!
further!to!show!associated!flora!alteration!is!
present!(cause/effect?)!
!  This!supports!rational!for!overgrowth!
syndrome!(so!called!dysbiosis)!
!  Is!dysbiosis!the!result!or!a!cause!for!digestive!
issues?!
!  Does!altered!diet!and!feeding!pattern!alter!
microenvironment?!
! 
! 
! 
Feingold:!Desulfovibrio!species!identified!in!ASD!
sources,!not!in!control!comparisons!(Anaerobe!
2010)!
Williams:!Sutterella!species!identified!in!children!
with!ASD!but!not!controls!(PLOS!2012)!
Parracho:!DoubleNblind!placeboNcontrolled!
crossover!trial!!using!Lactobacillus!Plantarium!in!
autism!reduced!clostridial!counts!and!improved!
stool!nature!(International!Journal!of!Probiotics!and!
Prebiotics!2010)!
! 
! 
Kang:!Reduced!Incidence!of!Prevotella!and!Other!
Fermenters!in!Intestinal!Microflora!of!Autistic!
Children!(PLOS!One!2013)!
Commonalities)from)the)microflora)so)far:)
diminished)diversity,)diminished)lactose)
fermenter)population,)?)Growing)concern)about)
specific)predominance)of)specific)Clostridial)
species))
!  Office!Hours!recently!launched!video!series!
on!AutismSpeaks!website!discussing!medical!
issues!and!autism.!Topics!discussed!included!
reflux,!sleep,!probiotics!!
!!!!!www.autismspeaks.org/siteNwide/officeNhours!
!  A!series!of!Cleveland!Clinic!CME!sessions!
discussing!medical!coNmorbidity!in!autism!
www.clevelandclinicmeded.com/online/webcasts/autismN
spectrumNdisorders/medicalNcomorbidities/!
!  Casein!Gluten!Soy….Elimination!diets!
!  Carbohydrate!Reduction!Diets:!Lactose!free.!
Specific!Carbohydrate!Diet,!Ketogenic!Diet,!
Paleo!Diet,!GAPS,!LGIT!
!  Chemical!Reduction!Diets:!Finegold!Diet!
TOPICS
!  Basic!Info!
!  What!are!you!seeking!to!treat?!
!  Which!is!best?!
!  Always!try!to!find!the!nutrition!from!food!
sources!
!  Unique!vitamin!supplementation!has!a!place!
!  NRFPT:!Not!ready!for!prime!time?!
!  What!is!known!on!the!topic?!
but!this!is!best!done!with!nutritionist!support!
and!some!testing!
!  Side!effects!are!common!and!multiply!with!
multiple!supplements!
! 
GI!issues!are!common!in!children!with!autism,!
frequency!over!the!general!population!requires!
further!study!
! 
The!pediatrician!needs!to!consider!the!child!with!autism!
in!a!medical!light!
! 
Until!proven!otherwise,!behaviors!should!be!considered!
medicallyNbased!
Profound!or!selfNinjurious!behaviors!may!require!
medical!or!behavioral!management.!We!believe!
continued!attention!to!underlying!medical!factors!may!
mitigate!ongoing!requirement!of!pharmacological!
behavioral!support!(risperidone!was!supported!for!short!
term!treatment!of!irritable!behaviors)!
! 
GI!conditions!in!autism!may!promote!worsening!
of!autistic!behaviors,!work!is!needed!to!determine!
if!any!GI!impact!on!causation!of!autism!
! 
! 
The!current!data!should!intensify!interest!in!the!
gut/brain!connections!in!autism.!Research!must!
be!supported!in!this!arena!of!autism.!
!!
!
My!MGH!Team!and!Mentors:!Harland!Winter,!Margaret!
Bauman,!!!!!Katherine!Murray,!Rafail!Kushak!!
!
My!Support:!Newman!Foundation,!Autism!Research!
Institute,!AutismSpeaks,!My!Family!
!
Hawaiian)‘Ohana:!Julianne!and!Don!King,!Megan!Liddell,!
Cynthia!Bartlett,!Lee!Ann!Tokuda,!Jeremy!King,)!Hawaii!
Autism!Foundation,!HMSA!Foundation,!Additional!partners!
in!caring!for!individuals!with!autism!in!the!Hawaii!
community!!