PHENYLKETONURIA

(PKU)

Phenylketonuria is a genetic disorder that occurs because of a

dysfunctional phenylalanine hydroxylase enzyme that is used to
convert phenylalanine to tyrosine, resulting in accumulation of
phenylalanine in the body that can cause mental retardation.
• It is an inborn error of phenylalanine (Phe) metabolism caused by the
deficiency of phenylalanine hydroxylase. This deficiency leads to the
accumulation of Phe and its metabolites in tissues and body fluids of
PKU patients. Some of the excess acumulated phenylalanine is
metabolized to phenylketones, which are excreted in the urine, giving
rise to the term phenylketonuria.
• The child has normal blood phenylalanine levels at birth; however,
levels increase after birth and can result in irreversible damage by 2
years of age if not detected and treated.
 SIGNS AND SYMPTOMS

• Vomiting
• Irritability and/or a red skin rash with small pimples
• Developmental delay
• Intellectual disability
• Depression by reducing brain levels of dopamine and serotonin
(neurotransmitters)
• Light eye, skin, and hair color due to high phenylalanine levels
interfering with production of melanin
• Musty or “mousy” body odor caused by phenyl acetic acid in the urine
or sweat.
• Mental retardation as early as 4 months of age
• Dry skin
• Macrocephaly
Neurological symptoms present in some untreated patients with PKU
include;
• Seizures
• abnormal muscle movements
• tight muscles
• increased reflexes
• involuntary movements or tremor
 CAUSES

• PKU is inherited in an autosomal recessive pattern.

• The risk is the same for males and females

• More than 300 different changes (mutations) in the PKU gene have
been identified. Different mutations result in varying degrees of PAH
enzyme activity, and therefore varying degrees of phenylalanine
elevation in blood, hence, the diet of each child must be adjusted to
the individual’s specific phenylalanine tolerance.
Pathophysiology of PKU

• Excess dietary phenylalanine (ie that not used for protein synthesis) is
normally converted to tyrosine by phenylalanine hydroxylase;
(tetrahydrobiopterin (BH4) is an essential cofactor for this reaction).
• When one of several gene mutations results in deficiency or absence
of phenylalanine hydroxylase, dietary phenylalanine accumulates.
• This results in neurological disturbances of varying degrees as the
brain is the main organ affected, possibly due to disturbance of
myelination.
• Although nearly all cases (98 to 99%) of PKU result from
phenylalanine hydroxylase deficiency, phenylalanine can also
accumulate if BH4 is not synthesized because of deficiencies of
dihydrobiopterin synthase or not regenerated because of deficiencies
of dihydropteridine reductase.
• Additionally, because BH4 is also a cofactor for tyrosine hydroxylase,
which is involved in the synthesis of dopamine and serotonin, BH4
deficiency alters synthesis of neurotransmitters, causing neurologic
symptoms independently of phenylalanine accumulation.
• Some of the excess phenylalanine is metabolized to phenylketones,
which are excreted in the urine, giving rise to the term phenylketonuria.
• The degree of enzyme deficiency, and hence severity of
hyperphenylalaninemia, varies among patients depending on the
specific mutation.
• Intellectual disability in PKU is a direct result of elevated levels of
phenylalanine in the brain which causes the destruction of the fatty
covering (myelin) of individual nerve fibers. It can also cause depression
by reducing brain levels of dopamine and serotonin (neurotransmitters).
• Untreated infants with PKU tend to have unusually light eye, skin, and
hair color due to high phenylalanine levels interfering with production
of melanin
• They may also have a musty or “mousy” body odor caused by phenyl
acetic acid in the urine or sweat.
 Assessment and Diagnostic Findings

• Guthrie inhibition assay test. This screening uses blood from a simple heel prick; the test
is most reliable after the newborn has ingested some form of protein; the accepted
practice is to perform the test on the second or third day of life.
• Plasma phenylalanine. A qualified laboratory should measure plasma phenylalanine and
tyrosine; screening for PKU includes determination of phenylalanine levels, the standard
amino acid analysis done by means of ion exchange chromatography or tandem mass
spectrometry.
• Urine tests. Results of urine tests (i.e, ferric chloride test) may be negative in the first
month of life and are rarely used in current practice.
• Magnetic resonance imaging. Cranial MRI studies may be indicated in older individuals
who have poor dietary control and are experiencing deficits in motor or cognitive
function, or when there are behavioral, cognitive, or psychiatric concerns.
 MANAGEMENT

• The goal of treatment for PKU is to keep plasma phenylalanine levels

within 120-360Mmol/L (2-6 mg/dL).
• This is generally achieved through carefully planned and monitored
diet.
Limiting the child’s intake of phenylalanine must be done cautiously
because it is an essential amino acid.

A carefully maintained diet can prevent intellectual disability as well as

neurological, behavioral, and dermatological problems.
Studies have repeatedly demonstrated that children with PKU who are
treated with a low phenylalanine diet before the age of three months
do well, with an IQ in the normal range.
Treatment must be started at a very young age or some degree of
intellectual disability may be expected. However, even some late-
treated children have done quite well.
• Frequent monitoring of plasma phenylalanine levels is required;
recommended targets for all children are between 2 mg/dL and 6
mg/dL (120 to 360 mmol/L).
• Dietary planning and management need to be initiated in women of
childbearing age before pregnancy to ensure a good outcome for the
child.
DIETARY MANAGEMENT

• Dietary treatment is required; treatment consists of dietary

restriction of phenylalanine often with tyrosine supplementation.
• Phenylalanine-free formulas. A formula low in phenylalanine should
be started as soon as the condition is detected; Lofenalac and Phenyl-
free are low phenylalanine formulas; best results are obtained if the
special formula is started before the newborn is 3 weeks of age.
• Restricted diet. A low phenylalanine diet is a very restricted one;
foods to be omitted are breads, meat, fish, dairy products, nuts, and
legumes; the child remains on the diet at least into early adulthood,
and it may even be recommended indefinitely.
• Amino acid supplementation. Other essential amino acids are
supplemented using various medical foods, and vitamin, mineral, and
other micronutrients are followed closely; stringent phenylalanine-
restricted diets have been reported to cause deficiencies of iron, zinc,
selenium, and other nutrients and essential amino acids in patients
with PKU.
• Avoidance of aspartame. Aspartame must also be avoided;
phenylalanine is one of the primary components of aspartame; it is
found in many artificially sweetened foods and soft drinks, as well as
some vitamins and medicines; a 12-oz can of aspartame-sweetened
diet drink contains approximately 105 mg of phenylalanine (ie, 25-
50% of the usual daily intake).
Pharmacological Management

• Sapropterin. It is a commercially available, FDA-approved form of the

tetrahydrobiopterin (BH4) cofactor. (1 to 5 mg/kg orally 3 times daily)

• Enzyme therapy. An alternative enzyme therapy for PKU in clinical

trials involves the use of an injectable form of phenylalanine
ammonium lyase, an enzyme capable of substituting for
phenylalanine hydroxylase (PAH); this therapy is currently under
investigation for the potential treatment of patients with PKU who do
not respond to BH4
Nursing Assessment

• Assessing a child with PKU should include:

• Nutritional history. Upon birth of the newborn with PKU, assess if he
has consumed any formula which is not phenylalanine-free to identify
measures to be made.
• Physical examination. Assess the newborn for any manifestations that
may indicate emergency care.
Nursing Diagnoses

• Based on the assessment data, the major nursing diagnosis are:

• Imbalanced nutrition: less than body requirements related to
restrictive diet.
• Impaired skin integrity; related to scratching at the perineal area
secondary to eczema.
• Anxiety related to the disorder and adverse reactions that the infant
may experience.
• Risk for injury related to convulsions.
• Altered thought process related to poor intellectual abilities.
• Deficient knowledge related to the disorder and the care of the
newborn with PKU.
Nursing Objectives

• The caregiver will be able to provide the appropriate nutritional needs

of the infant.
• The infant will be free from injury.
• The infant’s skin integrity will be intact and free from infection.
• The caregiver will be knowledgeable enough about the disorder and
in managing the infant with PKU.
Nursing Interventions

• Diet. Inform family caregivers of the foods that they should avoid giving the
infant once he is allowed to take solid foods; special formulas are also indicated
instead of regular formulas or breastmilk, such as Lofenalac and Phenyl-free
formulas.
• Emotional support. Offer support to the family emotionally especially after the
diagnosis so they could cope with the shock, anxiety, and stress.
• Health education. Educate the family on the disease process and how they
could help the child grow as normally as he could; if a child’s phenylalanine
control is kept within the acceptable range, growth and development will not be
affected.
• Safety. In case of convulsions which may occur in a child with PKU, educate the
family caregivers on how to handle the child with safety being the priority.
 Evaluation
• Goals are met as evidenced by:
• The caregiver provided the appropriate nutritional needs of the
infant.
• The infant is free from injury.
• The infant’s skin integrity is intact and free from infection.
• The caregiver is knowledgeable enough about the disorder and in
managing the infant with PKU.