Phenylketonuria

Martha Blair Gwaltney

Medical Genetics
R Ostrowski, PhD. and L. McNally, M.S.
July 1, !""!
Martha Blair Gwaltney
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#$stract
Phenylketonuria (PKU) is a disease in which one cannot metabolize the amino
acid phenylalanine normally !t is an autosomal recessi"e trait so there#ore both parents
must be $silent carriers% !# not treated& the disease can cause se"ere problems& including
mental retardation 'owe"er& due to newborn screening& patients can be diagnosed early
(his allows #or the treatment o# PKU& which is a strict low phenylalanine diet that must
begin early in li#e and be well maintained !# treatment is #ollowed& PKU patients can
li"e a normal li#e
Martha Blair Gwaltney
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%ntroduction
*r +sb,orn -olling& #rom .orway& disco"ered Phenylketonuria in /0)1 (see
#igure /) + woman brought her two se"erely mentally retarded to *r +sb,orn because
she had noticed a peculiar smell coming #rom them (he woman had been to many
doctors but none had been able to help Unlike most doctors at the time& *r +sb,orn had
knowledge o# chemistry and biochemistry 'e e2amined the two children& a girl si2 and
a hal# years o# age and a #our3year3old boy *r +sb,orn #ound nothing o# importance in
the clinical e2amination& but took urine samples 'e tested the urine with #erric chloride&
a chemical used to detect ketones in diabetics .ormal urine stays a brownish color when
#erric chloride is added while the presence o# ketones turns urine purple or burgundy
4urprisingly& the children5s urine turned a dark green when tested (his had ne"er been
seen be#ore +#ter doing much testing and researching& *r +sb,orn realized that
phenylpyru"ic acid was responsible and was being e2creted in the urine (hrough #urther
testing& *r +sb,orn #ound that the patients had "ery high le"els o# phenylalanine (his
was the beginning o# Phenylketonuria (PKU) (.ational PKU news)
PKU a##ects / in /6&666 babies (hese babies are predominantly 7aucasians and
8ast +sians (he disease is e2ceedingly rare in +#ricans (.ational PKU news)
Phenoty&ic Milestones and Dia'nostic (echni)ues
PKU is a rare& inherited metabolic disease resulting in mental retardation and
other neurological problems when treatment is not started within the #irst #ew weeks o#
li#e (.ational 9rganization #or :are *isorders; PKU news) <hen two carriers concei"e
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there is a 2= > chance #or each pregnancy that a PKU baby will be born 'owe"er& the
chance o# two carriers mating is / in 2&=66 (.ational PKU news)
PKU is the result o# an inborn error o# metabolism& arising #rom the absence o# a
single enzyme (.!') (his enzyme& phenylalanine hydro2ylase (P+')& is produced in
the li"er P+' normally con"erts the amino acid phenylalanine to another amino acid&
tyrosine (.ational PKU news) P+' works by grabbing an o2ygen atom and trans#erring
it to the phenylalanine molecule + nearby hydrogen ion then attaches to the o2ygen
#orming tyrosine + mutation to the P+' gene on the long arm (?) o# chromosome /2
results in an enzyme that does not work properly and there#ore the body cannot
metabolize phenylalanine (@osiah Macy& @r -oundation)
Phenylalanine plays an important role in a metabolic pathway Genes in the
metabolic pathway are always turned o## until a precursor turns them on Phenylalanine
works as a precursor to turn on gene /& which creates P+' to produce tyrosine (he
presence o# tyrosine then turns on gene 2& which produces another enzyme to continue
the pathway and cause other genes to turn on + #inal product in the pathway is the
pigment melanin !n PKU& a de#ect in gene / pre"ents phenylalanine5s con"ersion to
tyrosine resulting in phenylalanine building up in the body (@osiah Macy& @r -oundation;
see #igure 2)
*isruption o# the metabolic pathway causes many problems 82cess
phenylalanine in the brain poisons neurons and leads to mental retardation (@osiah Macy&
@r -oundation) <hen not treated& PKU patients may ha"e a smaller than normal head
(hey also ha"e broad shoulders& a stooping #igure and a spastic gait 82cess
phenylalanine creates a musty odor and a de#iciency in tyrosine leads to lighter skin and
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hair because the melanin pathway is a##ected (he skin disorder eczema is common in
PKU patients (@osiah Macy& @r -oundation and .ational PKU news) 9ne may also
notice hyperacti"ity& aggressi"e beha"ior& epilepsy& seizures& and psychiatric disturbance
(.!') 4ymptoms o# PKU are typically absent in newborns 'owe"er& in rare cases a
newborn may show signs that include being abnormally drowsy and listless (hey may
also e2perience di##iculties #eeding (.ational 9rganization #or :are *isorders)
(he diagnosis #or PKU is #airly simple *octors per#orm newborn screening by
pricking the heel or hand o# the newborn to collect a #ew drops o# blood on a piece o#
#ilter paper (aka Guthrie cards) + cut out o# the bloodspot is placed on a plate o#
bacteria that cannot grow without phenylalanine !# the bacteria grow& phenylalanine is
present& possibly indicating PKU (he se"erity o# PKU depends on the size o# the halo o#
bacteria + larger halo o# bacteria indicates a higher amount o# phenylalanine present
9ther blood tests must be conducted to determine i# the high le"el o# phenylalanine is due
to PKU or a de#ect in another protein A B'1 A that causes the same symptoms (.ational
PKU news)
Discussion
(he main treatment #or PKU is to begin a "ery strict diet early in li#e and maintain
that diet well (his diet eliminates all #oods that are high in protein +ll protein contains
phenylalanine and is there#ore dangerous to a PKU patient -oods that cannot be eaten
includeB meat& #ish& poultry& milk& eggs& cheese& ice cream& legumes& nuts& and products
containing #lour + synthetic #ormula is used as a nutritional substitute +lthough it was
once belie"ed that the diet could be discontinued around the ages o# C3/6& it is now said
that the diet should be maintained #or a li#etime (he diet is especially important to
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pregnant women who ha"e PKU !# these women consume phenylalanine during their
pregnancy& the buildup can become "ery dangerous to their baby (he result could be as
se"ere as mental retardation (@osiah Macy& @r -oundation; .ational 9rganization #or
:are *isorders; and .ational PKU news)
*onclusion
PKU is a serious disease 'owe"er& due to newborn screening carried out in
e"ery state in +merica& PKU babies can li"e a normal li#e (here is a #airly simple
treatment #or phenylketonuria +ll one has to do is #ollow a low phenylalanine diet !#
the patient does not ha"e a bad case o# PKU& then the diet is not that e2clusi"e 8"en
though phenylketonuria can be a se"ere disease& patients that ha"e it are li"ing a li#e ,ust
like anyone else thanks to today5s diagnostic techni?ues and treatments
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Re+erences
@osiah Macy& @r -oundation $Phenylketonuria% Ewww.your'enesyourhealth.or'F
(+ccessed DGCG62)
.ational 9rganization #or :are *isorders $Phenylketonuria (PKU)%
Ewww.rarediseases.or'F (+ccessed DGCG62)
.ational PKU .ews $+bout PKU% Ewww.&kunews.or'F (+ccessed
DGCG62)
.!' (.ational !nstitutes o# 'ealth) Ewww.'eneclinics.or'F (+ccessed DGCG62)
Ewww.che,.ucla.edu-.alice-che,istry-de&t-+aculty-&ictures-P/01Sche,e.'i+F
(+ccessed DGCG62)
Martha Blair Gwaltney
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#&&endi2
3i'ure 1
*r +sb,orn -olling disco"ered PKU in /0)1 (PKU news)
3i'ure !
Phenylalanine works as a precursor to turn on gene /& which creates P+' to produce
tyrosine (he presence o# tyrosine then turns on gene 2& which produces another enzyme
to continue the metabolic pathway <hen phenylalanine does not work properly& it does
not con"ert to tyrosine and instead becomes a buildup o# phenylpyru"ic acid (his in
return causes PKU
(wwwchemuclaeduGIaliceGchemistryGdeptG#acultyGpicturesGPKU34chemegi#)