THE PSYCHOLOGY OF PKU and ALLIED DISORDERS AND THE BOSTON MARATHON

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THE PSYCHOLOGY OF PKU and ALLIED DISORDERS(AND
THE BOSTON MARATHON)

• SUSAN WAISBREN, PHD
• CHILDRENS HOSPITAL, BOSTON

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Key Points
Metabolic control is important The first 6 years
are critical A metabolic disorder changes the
person and the family, but not necessarily in a
negative way.
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BEFORE THE RACE

• Who you are
• (age, gender, body type)
• Prior experiences
• Training

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BEFORE THE RACE PRENATAL FACTORS

• Much is determined prior to the start day
• Parental IQ (correlates .42 with child IQ)
• Demographic circumstances
• Genes
• Pregnancy

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THE STARTING LINE

• The weather
• How you feel
• How long you had to wait at the porta-potty line
• The vibes of the crowd
• Which corral you start in

26844
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THE STARTING LINE FOR CHILDREN WITH PKU

• Birth complications and APGAR
• Maturity of digestive system
• How the family accepts the diagnosis
• The home environment
• Maternal bonding

Murray L, et al, Child Dev. 1996 67
2512-2526.
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FIRST FEW MILES - SWEET
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AGES 0-2 YEARS

• Diet usually pretty smooth sailing
• Developmental course usually as expected
  (milestones reached on time)
• If children are having difficulties during this
  period, it may be that something else is going on

REMEMBER A DQ IS NOT AN IQ
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AGE 18 MONTHS OR SO

• PERIOD OF HUGE COGNITIVE SHIFT
• - Language
• Imagination
• Anxiety
• USE WORDS EXPLAIN
• EVERYTHING!

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3-year-olds Skills at this age.

• TIME OF SHIFT IN MOTOR SKILLS
• Draw lines and a circle
• Jump
• TIME OF SHIFT IN
• LANGUAGE SKILLS
• Speak clearly in sentences
• Understand yes-no foods

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EARLY CHALLENGES (AGES 3 YEARS)

• Sometimes a cramp if start too fast.
• 3 year-olds have very little self-control, but
  are at an age when prefer to do things their
  way. Therefore, we need to keep demands at age
  appropriate level.
• If metabolic control lost at this age, outcome
  is poor
• EARLY INTERVENTION THERAPY HELP

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MILES 4-6 FOR THE RUNNER

• Attain a rhythm
• Feeling calmer
• Can finally look around
• and notice surroundings

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MILES 4-6 (ages 4-6 YEARS)

• Diet usually a straightforward process. Rules
  are good and understandable. There is right and
  wrong.
• Social growth usually goes pretty well.
• Sometimes is separation anxiety
• Sometimes is delay in fine motor
• Many repeat kindergarten

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• Good time to introduce memory tasks
• Good time to teach categories
• IQ Stabilizes
• Skills
• Counting phes
• Drawing foods
• Writing a few letters (name)

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BLOOD PHE AND IQ ARE CORRELATED IN PATIENTS WITH
PKU
Waisbren SE, et al. Mol Genet Metab.
2007926370.
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MILE 7-11 FOR THE RUNNER

• In the ZONE
• Not paying much attention to the surroundings
• Adjust pace depending on how you feel
• A few hills, but these are forgotten as more
  miles lie behind you
• UNLESS you didnt eat enough breakfast, train
  well enough, or take care of the small blisters

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AGES 7-11 YEARS IN PKU

• Latency period social connections critical
• Period of Concrete Operations (can think
  abstractly for the first time)
• Academic demands are suddenly harder to meet
  require application of knowledge (no longer rote
  learning)
• Not uncommon to experience
• resistance to treatment

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MYELIN
White matter contains nerve fibers surrounded by
myelin
Image from http//kvhs.nbed.nb.ca/gallant/biology
/schwann_myelin.html
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WHITE MATTER DEFICITS

• Individuals with PKU have abnormal white matter
• White matter abnormalities may reduce speed of
  processing leading to neurocognitive deficits
  observed with PKU
• What looks like Attention Deficits may be
  response to slow processing speed.

Anderson P, et al. Devel Neuropsychol.
200732(2)645-668.
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MILES 12-15 FOR THE RUNNER

• Hurray for Wellesley College girls, who can be
  heard screaming one mile away!
• Hearing those girls spurs you on!
• Halfway there, you
• may re-adjust your pace

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AGES 12-15 YEARS IN PKU

• Begin to enter stage of formal operations
  ability to re-adjust life views
• Social support becomes critical.
• Very difficult time to maintain treatment.
• If well treated earlier, some research suggests
  that deficits related to poor adherence at this
  age are subtle.
• Slower information processing is apparent in
  almost all children with PKU at this age.

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DOPAMINE EXECUTIVE FUNCTION, EMOTION AND SOCIAL
BEHAVIOR

• Neurotransmitter related to attention, mood, and
  movement
• Precursor to norepinephrine, epinephrine, and
  other neurotransmitters

Image from http//nobelprize.org/nobel_prizes/medi
cine/laureates/2000/press.html
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DOPAMINE IS SYNTHESIZED FROM TYROSINE THAT IS
CONVERTED TO DOPAMINE
Blood Brain Barrier
Periphery (mostly liver)
Brain
PAH
TH
AADC
Phenylalanine
Dopamine
Tyrosine
L-dopa
Tyrosine
BH4
BH4
BH4 tetrahydrobiopterin PAH phenylalanine
hydroxylase TH tyrosine hydroxylase AADC
aromatic amino acid decarboxylase
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EXECUTIVE FUNCTIONING DEFICITS
Planning Organization Memory Attention Problem
Solving
Packman W, et. al. Executive functioning in
children and adolescents with phenylketonuria.
Clin Genet. 2007 213-8.
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COMING OF AGE
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MILES 16-20 FOR THE RUNNER

• Time of transitions You leave the support of
  the Wellesley girls, cross over the highway, head
  toward the home stretch.
• The pack is more dispersed, you feel more on your
  own. Its easy to feel discouraged.
• Sometimes you find a few new friends to accompany
  you on the journey

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AGES 16-20 IN PKU

• High school can be discouraging executive
  function demands are great
• Peers exert pressure to conform
• Leaving for college leaves some students feeling
  alone
• Most college students stop diet or experience
  period of poorer adherence

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CHALLENGES WHEN PHE LEVELS ARE HIGH

• Low motivation
• Depression
• Anxiety
• Reading comprehension poor or laborious
• Attention Deficits (Inattentive type)
• Math and Science particularly difficult
• Poor executive functioning

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ADOLESCENTS ADULTS

• Elevated phe exerts global effect slowing
  performance and mental processing speed

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HEARTBREAK HILL- MILES 20-21

• Slow but steady rise in terrain
• Sometimes cant even think straight anymore
  realize you need to be careful
• Know that you need nourishment, but you have
  troubles getting
• anything down

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AGES 20-21 IN PKU

• The realization that need to resume dietary
  treatment comes again
• Recognize the very real problems in
  concentration, completing assignments, and
  keeping relationships

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HITTING THE WALL Miles 21-25

• The hardest miles in the whole race because
  nothing prepares you for this.
• Suddenly, the crowds thin, supports are much
  less, and it is up to you to finish the race.
• You wont quit, youll walk or
• even crawl to the finish

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TRANSITION TO ADULT CARE

• Estimated adults with PKU (ages 21-45 years)
  8,400 (based on 350 per year)
• Estimated 10 lost to follow-up
• Adult metabolic clinics in United States
• None in 1998
• Maybe 4 now Seattle, Atlanta, Pittsburg, Boston

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Genetic and NBS Collaboratives

• National Metabolic and Genetic Conditions
  Transition Work Group
• WWW.WADSWORTH.ORG/NEWBORN/NYMAC/INDEX

Genetics and Metabolism Psychology Network
(www.GMPsych.org)
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AGES 21-25 IN PKU

• Graduating college, finding work, sorting out
  relationships, moving back home or away,
  remembering the diet
• Family and healthcare providers just dont know
  how great a toll it takes.
• Intellectual functioning deficits are easier to
  hide, but are still there.

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THE RISKS

• High phe levels lead to
• Inattention
• Depression
• Anxiety
• Emotional ups and downs
• General slowing of information processing
• Return to diet does not change IQ, but may help
  symptoms especially processing speed, executive
  functioning and mood.

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RECOMMENDATIONS YOUTH ADULTS
SOCIAL SUPPORT POSITIVE ATTITUDES MANAGEABILITY
Finkelson L, Bailey I, Waisbren SE. J Inherit
Metab DIs. 2001 24 515-516.
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THE FINISH LINE MILE 26

• There is this small little hill that seems like
  a mountain and then you are inside the police
  barriers and there are thousands of people lining
  the street cheering.
• You feel awesome.

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BUT, FOR ADULTS WITH PKU

• ITS A TRIATHLON!
• DIET FOR LIFE
• MATERNAL PKU
• SECURING INSURANCE

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TAKE HOME MESSAGES

• Metabolic Control is important
• The first six years are critical
• A metabolic disorder changes the person and the
  family, but not necessarily in a negative way.

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THANK YOU