textfiles/drugs/amac-pku

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From: grx0644@uoft02.utoledo.edu
A while back, there was alot of comments on PKU. Some comments were correct,
some were just plain wrong. I decided to d/l an artical on PKU and post it for
those interested.
PHENYLKETONURIA (PKU)
From the
PEDIATRIC INFORMATION RESOURCE CENTER
Rainbow Babies & Childrens Hospital
2101 Adelbert Road
Cleveland, Ohio 44106
DEFINITION:
Phenylketonuria (PKU) is a genetic disorder that is
characterized by an inability of the body to utilize the
essential amino acid, phenylalanine. Amino acids are the
building blocks for body proteins. 'Essential' amino acids
can only be obtained from the food we eat as our body does
not normally produce them. In 'classic PKU', the enzyme
that breaks down phenylalanine phenylalanine hydroxylase, is
completely or nearly completely deficient. This enzyme
normally converts phenylalanine to another amino acid,
tyrosine. Without this enzyme, phenylalanine and its'
breakdown chemicals from other enzyme routes, accumulate in
the blood and body tissues. Although the term
'hyperphenylalaninemia' strictly means elevated blood
phenylalanine, it is usually used to describe a group of
disorders other than classic PKU. These other disorders may
be caused by a partial deficiency of the phenylalanine
breakdown enzyme or the lack of another enzyme important to
the processing of this amino acid. A normal blood
phenylalanine level is about 1 mg/dl. In classic PKU,
levels may range from 6 to 80mg/dl, but are usually greater
than 30mg/dl. Levels are somewhat less in the other
disorders of hyperphenylalaninemia. Chronically high levels
of phenylalanine and some of its breakdown products can
cause significant brain problems. Classic PKU is the most
common cause of high levels of phenylalanine in the blood
and will be the primary focus of this topic sheet.
INCIDENCE:
Classic PKU and the other causes of hyperphenylalaninemia
affect about one of every 10,000 to 20,000 Caucasian or
Oriental births. The incidence in African Americans is far
less. These disorders are equally frequent in males and
females.
CAUSE:
PKU and the other causes of hyperphenylalaninemia are
inherited in a recessive fashion. This means an affected
person inherited two traits for the disorder (e.s., one from
each parent). A person with one trait for the disorder, is
called a 'carrier' for PKU. Carriers do not have symptoms
of the disorder.
SYMPTOMS:
Infants with PKU appear normal at birth. Many have blue
eyes and fairer hair and skin than other family members.
Currently, most symptoms of untreated PKU are avoided by
newborn screening, early identification, and management.
(see Treatment Section)
The following describes untreated PKU symptoms-currently a
rarity:
About 50% of untreated infants have early symptoms, such as
vomiting, irritability, an eczema-like rash, and a mousy
odor to the urine. Some may also have subtle signs of
nervous system function problems, such as increased muscle
tone, and more active muscle tendon reflexes. Later, severe
brain problems occur, such as mental retardation and
seizures. Other commonly noted features in untreated
children include: microcephaly (small head), prominent
cheek and upper jaw bones with widely spaced teeth, poor
development of tooth enamel, and decreased body growth.
TREATMENT:
Every state now screens the blood phenylalanine level of all
newborns at about 3 days of age. This test is one of
several newborn screening tests performed before or soon
after discharge from the hospital. Usually, a few drops of
blood are obtained by a small prick on the heel, placed on a
card, and then sent for measurement. If the screening test
is abnormal, other tests are needed to confirm or exclude
PKU. Newborn screening allows early identification and
early implementation of treatment.
The goal of PKU treatment is to maintain the blood level of
phenylalanine between 2 and 10 mg/dl. Some phenylalanine is
needed for normal growth. This requires a diet that has
some phenylalanine but in much lower amounts than normal.
High protein foods, such as: meat, fish, poultry, eggs,
cheese, milk, dried beans, and peas are avoided. Instead,
measured amounts of cereals, starches, fruits, and
vegetables, along with a milk substitute are usually
recommended. Phenylalanine free formulas are available for
all age groups. In some clinics, a phenylalanine
'challenge' may be suggested to evaluate whether or not the
child continues to require a low phenylalanine diet. This
test identifies those few persons with a transient or
'variant' form of the disorder. However, most authorities
currently recommend lifelong dietary restriction of
phenylalanine for individuals with classic PKU, in order to
promote maximal development and cognitive abilities. Trying
to reinstitute the PKU diet after a period of 'relaxation'
to a regular diet, has been difficult for many individuals.
Periodic phenylalanine blood level measurement, and the
guidance of a nutritionist and other members of the health
care team, allow individuals and families to work toward
consistently maintaining the blood level in the desirable
range.
Fever and illness can cause normal body proteins to break
down, the liberation of the body's own amino acids, and
thus, a rise of the blood phenylalainine level. The
physician and nutritionist can suggest dietary changes to
help maintain levels in the desirable range during illness.
Medical follow-up often involves periodic developmental
screening. This checks for the expected normal development
over time, and allows early recognition and intervention for
problems.
LIMITATIONS:
None for treated individuals.
COURSE:
Maintaining phenylalanine blood levels in the recommended
range maximizes the ability of individuals with PKU to reach
their potential for normal development and lifespan.
Authorities currently recommend that women with PKU who are
of child bearing age, closely adhere to the low-
phenylalanine diet and monitor phenylalanine levels before
conception and throughout pregnancy. The risk of
spontaneous abortion, mental retardation, microcephaly,
and/or congenital heart disease in the child is high if
Mother's blood phenylalanine is poorly controlled.
BEHAVIORAL/EDUCATIONAL CONCERNS:
The presence of a chronic condition may influence one's
emotional development. In addition, lifestyle adjustments
to accommodate more frequent doctor visits, and dietary
restrictions may be required and impact day to day
activities. These and other general issues are important to
understand and are discussed in the accompanying topic sheet
for "Chronic Illness".
The following information addresses PKU specifically:
Untreated PKU can cause significant brain problems including
retarded mental development. Current screening for PKU in
the newborn period has made unrecognized PKU a rare
occurance. With good dietary control, the potential effects
of PKU on development are minimized. However, recent
studies indicate that loss of dietary control in childhood
can interfere with cognitive development. These studies
support the idea that individuals with PKU should maintain
good dietary control throughout their lifetime. If problem
areas in development are suspected, this should be shared
with the parent so that an evaluation may be done and
intervention can be instituted.
It is important that all community personnel who work with
individuals with PKU be aware of the dietary requirements
and restrictions. The parent and/or nutritionist can
suggest appropriate and allowable snack and mealtime foods
outside the home. Supporting appropriate dietary habits,
while minimizing attention to dietary differences is
important. It is also important to be available to the
individual should he or she wish to share concerns or
feelings about being 'different' from peers. If persistent
difficulty adhering to the dietary regimen is noted, the
parent should be informed so that he/she and the medical
team can address this issue further.
Because blood phenylalanine levels are dependent on dietary
control, insufficient phenylalanine intake may cause levels
to be too low for growth and body functions. Low levels can
cause mental and physical sluggishness, loss of appetite,
anemia, rashes, and diarrhea. If these symptoms are
suspected, the parent should be contacted and arrangements
made for a physician evaluation.
POTENTIAL EMERGENCIES:
None.
RESOURCES/REFERENCES:
"Living with PKU" A publication from:
Inherited Metabolic Diseases Clinic
University of Colorado
Health Sciences Center
Denver, Colorado 80260
Distributed by: Mead Johnson Nutritionals
Evansville, Ill. 47721
This booklet contains an extensive bibliography for parents
and children with PKU.
National PKU News
7760 Ridge Drive N.E.
Seattle, WA 98115
Pediatric Endocrinology and Metabolism
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
(216) 844-3661
Dr. D. Kerr M.D. and Ms. J. McConnell - Nutritionist
Provides medical evaluation and coordinates long term
follow-up for children and families with PKU.
Referrals to clinics in the Cleveland metropolitan area that are
nearer to you may be obtained from your physician, Interlink at
the Achievement Center for Children (216) 795-7100, or through
Pediatric Endocrinology at Rainbow.
Rudolph, A.M., Hoffman, JIE, Pediatrics, 18. Appleton and
Lange, Norwalk, Conn., Los Altos, Calif. 1987, p. 239-242.
Behrman, R.E., Vaughan, V.C. and Nelson, W.E., Pediatrics,
13. W.B. Saunders, Philadelphia, PA. 1987, p. 280-282.
Roh, F., Friedman, E.G., Koch, R.: Maternal PKU. Metabolic
Currents. Vol I. No I: 1-8, 1988.
Smith, I., Beasley, M.G., Wolff, OH, Ades, E.A.: Behavior
Disturbance in 8-year-old children with early treated
phenylketonuria. The Journal of Pediatrics, 112:403-408,
March 1988.
Seashore, M.R., and others: Loss of Intellectual Foundation
in children with phenylketonuria After Relaxation of Dietary
Phenylalanine Restriction. Pediatrics 75:226-232, February
1985.
Michals, K, and others: Return to Diet Therapy in Patients
with Phenylketonuria. The Journal of Pediatrics, 106:933-
936, June 1985.
Holtzman, N.A., and others: Loss of Dietary Control in
Phenylketonuria. The New England Journal of Medicine
314:593-598, March 6, 1986.
Information contained in this topic sheet from PIRC is available
to the families and community personnel who care for children
with special needs, with the intent to provide general topic
information only. We strongly encourage direct contact with each
child's physician for specific questions regarding care,
medications, activity limitations and other concerns that may
arise.
PIRC is a service provided by Rainbow Babies and Childrens
Hospital, funded by the following foundations:
Bingham Foundation
Cleveland Foundation
George Gund Foundation
Thomas White Foundation
and NEC Computer INC.