EDUCATIONAL OBJECTIVES
14. Appropriate awareness of the
risks to infants born to mothers
with hyperphenylalaninemia (Re-
cent Advances, 85/86).
74. Appropriate knowledge to
counsel parents regarding the use
of phenylalanine-free diet in chil-
dren with phenylketonuria, partic-
ularly the age for discontinuing di-
etary precautions (Recent Ad-
vances, 85/86).
pediatrics in review #{149} vol. 7 no. 9 march 1986 PIR 269
Phenylketonuria-- 1986
Harvey L. Levy, MD, FAAP*
Phenylketonuria (PKU) has been
aptly described as the “epitome of
human biochemical genetics.” In so
distinguishing PKU among the many
metabolic disorders now known,
Scriver and Clow identified several
categories in which this inborn error
of metabolism is singularly prominent.
First and foremost, PKU represents a
fusion of effort between public health
and genetics. It is the major genetic
disorder in which treatment can pre-
vent the clinical expression of disease
and for which routine biochemical
screening of newborn infants was de-
veloped. It remains the model for
such screening. Second, PKU is the
prime example of the importance of
understanding as completely as pos-
sible the biochemical basis of a met-
abolic disorder. The detailed under-
standing of phenylalanine metabolism
that arose from studies spawned by
PKU led to the recognition of “new”
metabolic disorders that relate to
SPKU in their capacity to increase the
phenylalanine level but that involve a
different category of metabolism and
require very different treatment.
Third, PKU represents an important
link between obstetrics and pecliat-
rids. The threat to the fetus from PKU
in the pregnant woman (maternal
PKU) must be met by special dietary
care throughout the pregnancy. This
is, perhaps, only the first of other
maternal inborn errors that will re-
quire similar intervention during preg-
nancy.
The pediatrician is likely to confront
PKU on several levels. The newborn
screen may identify an infant with an
increased concentration of phenylal-
anine, thus introducing questions
such as whether this indicates PKU
or a transient abnormality. If the infant
has PKU, compliance with dietary
treatment may be an issue on which
the attending pediatrician and the
metabolic center involved in the care
of the child will interrelate. As the
child matures, questions such as 10,
S.Director, IEM-PKU Program, The Children s
Hospital; New England Regional Newborn
Screening Program, State Laboratory Institute;
Joseph P. Kennedy Jr Laboratories, Massachu-
setts General Hospital, Boston, MA 02114.
learning ability, and school perform-
ance may arise. Adolescent pediat-
rids may involve questions such as
maternal PKU.
This review will focus on what we
now know about PKU and on the
current issues regarding it, many of
which were not anticipated when
newborn screening and early treat-
ment of PKU began more than 20
years ago.
CLINICAL PICTURE
Late-Treated PKU
A 4-year-old boy was referred to
the Developmental Evaluation Clinic
because of mental retardation, au-
tism, and hyperactivity. He could not
speak and was not toilet trained. His
hyperactive behavior tended to be
aggressive and presented a formida-
ble problem to his family. He had
received several different medica-
tions for this hyperactivity. Only thior-
idazine (Mellaril) at a dose of 20 mg,
twice daily, had a calming effect. His
10 was 40. The neurologic assess-
ment revealed hyperactive deep ten-
don reflexes and hypertonia, as well
as mental retardation. He tended to
sit in a corner and rock back and
forth, seemingly oblivious to others.
His EEG was abnormal due to a
sharp-wave focus and slow spike-
waves in the frontal region. A blood
amino acid analysis requested for bio-
chemical assessment of the mental
retardation disclosed a phenylalanine
level of 40 mg/dL (normal <2 mgI
dL). Urine was positive for phenylke-
tones. These biochemical findings
identified him as having classic PKU.
He was born after an uneventful
pregnancy and delivery. According to
the hospital records, a blood sample
was obtained for screening when he
was four days old, but there was no
report of the results in his records.
When he was 1 2 days old, a routine
repeat newborn blood specimen was
obtained for PKU testing and was
reported as “negative.” During the
first few months of life, he was an
irritable baby and was thought to
have colic. By the time he was 9
months old, developmental delay was
evident in that he could not sit and
was socially unresponsive. At the age
of 1 8 months, he began to exhibit
autistic behavior. At this time he re-
ceived his first developmental evalu-
ation, and screening for PKU and hy-
pothyroidism was recommended.
Neither test was performed. As he
became older, the mental retardation
became more noticeable and the
hyperactivity more difficult to control.
After PKU was identified, he was
referred to a PKU clinic for dietary
therapy. It was recognized that a
phenylalanine-restricted diet at his
age would likely be futile because
compliance with the special formula
and the food restrictions might be
difficult and that even excellent met-
abolic control might not produce din-
ical improvement when begun after 3
years of age. He has adhered to the
diet, however, and has benefited, in
that the autistic behavior disappeared
soon after the diet began and his
development and behavior have sub-
stantially improved during the sub-
sequent 4-year period.
This unfortunate child illustrates
the mental retardation and other fea-
tures of brain damage that occur
when treatment for PKU is not initi-
ated in infancy. He also illustrates that
PKU can be missed in the newborn
screen and the need to retest for PKU
and other metabolic disorders in any
infant who shows signs of develop-
mental delay.
Early-Treated PKU
This girl came to attention when
her newborn screening blood speci-
at University of Michigan on June 18, 2015http://pedsinreview.aappublications.org/Downloaded from
