PHENYLKETONURIA

I. Description

• Phenylketonuria (PKU) is an autosomal recessive genetic disorder

characterized by a deficiency in the hepatic enzyme phenylalanine hydroxylase
(PAH).
• This enzyme is necessary to metabolize the amino acid phenylalanine
('Phe') to the amino acid tyrosine.
• When PAH is deficient, phenylalanine accumulates and is converted into
phenylpyruvate (also known as phenylketone), which is detected in the urine.
• 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.

II. 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.
III. 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.
• The following describes untreated PKU symptoms-currently a rarity: About 50%
of untreated infants have early symptoms, such as:
o vomiting
o irritability
o an eczema-like rash
o and a mousy odor to the urine
• Some may also have subtle signs of nervous system function problems, such as:
o increased muscle tone
o more active muscle tendon reflexes.
• Later, severe brain problems occur, such as mental retardation and seizures.
• Other commonly noted features in untreated children include:
o microcephaly (small head)
o prominent cheek and upper jaw bones with widely spaced teeth
o poor development of tooth enamel
o decreased body growth.

IV. Screening

Blood is taken from a two-week old infant to test for phenylketonuria

• PKU is normally detected using the HPLC test, but some clinics still use the
Guthrie test, part of national biochemical screening programs. Most babies in
developed countries are screened for PKU soon after birth.
• If a child is not screened during the routine newborn screening test (typically
performed at least 12 hours and generally 24–28 hours after birth, using samples
drawn by Neonatal heel prick), the disease may present clinically with seizures,
albinism (excessively fair hair and skin), and a "musty odor" to the baby's sweat
and urine (due to phenylacetate, one of the ketones produced). In most cases, a
 repeat test should be done at approximately 2 weeks of age to verify the initial test
and uncover any phenylketonuria that was initially missed.
• Untreated children are normal at birth, but fail to attain early developmental
milestones, develop microcephaly, and demonstrate progressive impairment of
cerebral function. Hyperactivity, EEG abnormalities and seizures, and severe
learning disabilities are major clinical problems later in life. A "musty or mousy"
odor of skin, hair, sweat and urine (due to phenylacetate accumulation); and a
tendency to hypopigmentation and eczema are also observed.
• In contrast, affected children who are detected and treated are less likely to
develop neurological problems or have seizures and mental retardation, though
such clinical disorders are still possible.

V. Pathophysiology

• Classical PKU is caused by a mutated gene for the enzyme phenylalanine

hydroxylase (PAH), which converts the amino acid phenylalanine to other
essential compounds in the body. Other non-PAH mutations can also cause PKU.
This is an example of genetic heterogeneity.

VI. Medical treatment

The Food and Drug Administration (FDA) has approved the drug sapropterin
(Kuvan) for treatment of some people with PKU. The drug is for use in combination
with a PKU diet. In approving the drug, the FDA directed that studies continue
regarding the drug's efficacy and long-term safety
VII. Nursing Management
- strict diet with very limited intake of phenylalanine, which is mostly
found in protein-rich foods.
- Frequent blood tests will monitor PKU levels as they change over
time, especially during childhood growth spurts and pregnancy.
- Formula for babies