From: [email-masked]

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.