Phenylketonuria (PKU), less commonly known as phenylalanine hydroxylase deficiency, is the most common inborn error of amino acid metabolism.

What is Phenylketonuria? 

  • Phenylketonuria is a recessive hereditary defect of metabolism that, if untreated, causes severe intellectual disability in most but not all affected children.
  • It results from an impaired ability to metabolize the essential amino acid phenylalanine, leading to accumulation in blood and tissues.
  • Commonly, classic PKU is considered to be present when untreated plasma phenylalanine levels exceed 20 mg/dL (1200 µmol/L) without treatment.
  • Elevated phenylalanine levels negatively impact cognitive function, and individuals with classic PKU almost always have intellectual disability unless levels are controlled through dietary or pharmacologic treatment.
  • In the United States and many other countries, PKU is detected by newborn screening, and individuals who are appropriately treated (e.g., with a diet low in phenylalanine and/or tetrahydrobiopterin) can have normal intelligence and lead a normal life.


In most patients, the classic type of PKU involves a deficiency of PAH that leads to increased levels of phenylalanine in the plasma (>1200 µmol/L; reference range, 35-90 µmol/L) and to excretion of phenylpyruvic acid (approximately 1 g/d) and phenylacetic acid in the urine.

  • PAH catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine.
  • The enzyme PAH crystallizes as a tetramer, with each monomer consisting of a catalytic domain and a tetramerization domain.
  • Examination of the mutations causing PKU reveals that some of the most frequent mutations are located at the interface of the catalytic and tetramerization domains.
  • A small percentage of children with elevated phenylalanine levels exhibit normal PAH levels but have a deficiency in synthesis or recycling of BH4.
  • This condition is sometimes termed malignant phenylketonuria (PKU) and can result from biallelic mutations in the GCH1, PCB1, PTS, or QDPR genes.
  • Thus, individuals with BH4 cofactor deficiency can have additional neurologic problems that are not fully corrected by dietary phenylalanine reduction alone, but often require additional treatments that may not be fully effective.

Statistics and Incidences

PKU frequency varies by population.

  • The prevalence in the general US population is approximately 4 cases per 100,000 individuals, and the incidence is 350 cases per million live births.
  • Approximately 0.04-1% of the residents in intellectual disability clinics are affected by PKU. A low incidence is reported in African Americans (1/50,000).
  • A high incidence is reported in Turkey (approximately 1 case in 2600 births), the Yemenite Jewish population (1/5300), Scotland (1:5300), Estonia (1:8090), Hungary (1/11,000), Denmark (1/12,000), France (1/13,500), the United Kingdom (1/14,300), Norway (1/14,500), China (1/17,000), Italy (1/17,000), Canada (1/20,000), Minas Gerais State in Brazil (1/20,000), and the former Yugoslavia (1/25,042).
  • A low incidence is reported in Finland (<1/100,000) and Japan (1/125,000).
  • PKU is most commonly diagnosed in neonates because of newborn screening programs.
  • Women with PKU must restrict their phenylalanine levels during pregnancy to avoid birth defects and intellectual disability in their infants. Untreated PKU during pregnancy can result in maternal PKU syndrome, which can variably cause congenital heart defects, brain malformations, microcephaly, and intellectual impairment.
  • In the United States, PKU is most common in whites; worldwide, PKU is most common in whites and Asians.

Clinical Manifestations

Most individuals with phenylketonuria (PKU) appear normal at birth.

Fair skin and hair due to impairment of melanin synthesis.
  • Fair skin and hair. This is the most characteristic skin manifestation, resulting from impairment of melanin synthesis; it can be striking in black and Japanese patients, although not all untreated patients are fair, and treated patients often have typical pigmentation
  • Eczema. Eczema is common, particularly in the perineal area.
  • Intellectual disability (ID). Severe, progressive retardation is characteristic.
  • Musty odor. There is a characteristic musty smell to the urine.
  • Epilepsy. Convulsions may also occur.
  • Eye abnormalities. Hypopigmentation may occur to untreated PKU.

Assessment and Diagnostic Findings

Most states require newborns to undergo a blood test to detect the phenylalanine level.

  • 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 (ie, 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.

Medical 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).

Pharmacologic Management

Patients who refuse dietary treatment may benefit to some degree from consuming large neutral amino acids.

  • Sapropterin. Some patients with PKU experience significant lowering of plasma phenylalanine levels after administration of sapropterin, a commercially available, FDA-approved form of the tetrahydrobiopterin (BH4) cofactor.
  • 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 Management

Nursing care for a child with PKU involves the following:

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 diagnoses are:

Nursing Care Planning and Goals

The nursing care planning goals for a child with phenylketonuria are:

  • 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

The nursing interventions for a child with PKU are:

  • 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.
  • Guidance from a dietitian.  It is important that dietary advice is consistent; the child’s dietitian should, therefore, be the only person giving advice.
  • 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.


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.

Documentation Guidelines

Documentation in a child with PKU include:

  • Individual findings, including factors affecting, interactions, nature of social exchanges, specifics of individual behavior.
  • Intake and output.
  • Cultural and religious beliefs, and expectations.
  • Plan of care.
  • Teaching plan.
  • Responses to interventions, teaching, and actions performed.
  • Attainment or progress toward desired outcome.

Practice Quiz: Phenylketonuria

Here’s a 5-item quiz for Phenylketonuria study guide. Please visit our nursing test bank page for more NCLEX practice questions.

1. When newborns have been on formula for 36-48 hours, they should have a:


A. Screening for PKU.
B. Vitamin K injection.
C. Test for necrotizing enterocolitis.
D. Heel stick for blood glucose level.

1. Answer: A. Screening for PKU. 

  • Option: A: By now the newborn will have ingested an ample amount of the amino acid phenylalanine, which, if not metabolized because of a lack of the liver enzyme, can deposit injurious metabolites into the bloodstream and brain; early detection can determine if the liver enzyme is absent.
  • Option: B: Vitamin K injection is already given at birth.
  • Options: C&D: Option C and D are not necessary.

2. A new mother has some questions about phenylketonuria (PKU). Which of the following statements made by a nurse is not correct regarding PKU?

A. A Guthrie test can check the necessary lab values.
B. The urine has a high concentration of phenylpyruvic acid
C. Mental deficits are often present with PKU.
D. The effects of PKU are reversible.

2. Answer: D. The effects of PKU are reversible.

  • Option: D: The effects of PKU stay with the infant throughout their life.
  • Options: A, B, C: These are all correct about PKU.

3. Janae, who has PKU, just had a convulsion; which of the following would be the lowest priority when caring for her?

A. Observing and taking down data on all seizures.
B. Assuring safety and protection from injuring.
C. Assessing for signs and symptoms of increased intracranial pressure (ICP).
D. Educating the family about anticonvulsant therapy.

3. Answer: C. Assessing for signs and symptoms of increased intracranial pressure (ICP).

  • Option: C: Signs and symptoms of increased intracranial pressure (ICP) are not associated with seizure activity and therefore would be the lowest priority.
  • Option: A: Careful observation and documentation of convulsions provide valuable information to aid prevention and treatment.
  • Option: B: Safety is always a priority in the care of a child with seizure disorder because seizures may occur at any given time.
  • Option: D: Improper administration of and incomplete compliance with anticonvulsant therapy can lead to status epilepticus; thus education is a priority.

4. A female child with PKU, age 6, is brought to the health clinic for a routine checkup. To assess the child’s vision, the nurse should ask:

A. “Do you have any problems seeing different colors?”
B. “Do you have trouble seeing at night?”
C. “Do you have problems with glare?”
D. “How are you doing in school?”

4. Answer: D. “How are you doing in school?”

  • Option: D: A child’s poor progress in school may indicate a visual disturbance.
  • Options: A, B, C: The other options are more appropriate questions to ask when assessing vision in a geriatric patient.

5. Hydrocortisone cream 1% is given to a child with eczema. The nurse gives instruction to the mother to apply the cream by?

A. Apply a thin layer of cream and spread it into the area thoroughly.
B. Avoid cleansing the area before the application.
C. Apply a thick layer of the cream to affected areas only.
D. Apply the cream to other areas to avoid occurrence.

5. Answer: A. Apply a thin layer of cream and spread it into the area thoroughly.

  • Option: A: Topical corticosteroids are administered sparingly and rubbed into the area thoroughly.
  • Option: B: The area should be cleaned first before administration.
  • Options: C&D: Thick application and rubbing it on other areas will likely lead to systemic absorption.

See Also

Related topics to this study guide:

Further Reading

Recommended resources and books for pediatric nursing:
  1. PedsNotes: Nurse's Clinical Pocket Guide (Nurse's Clinical Pocket Guides)
  2. Pediatric Nursing Made Incredibly Easy
  3. Wong's Essentials of Pediatric Nursing
  4. Pediatric Nursing: The Critical Components of Nursing Care
Marianne is a staff nurse during the day and a Nurseslabs writer at night. She is a registered nurse since 2015 and is currently working in a regional tertiary hospital and is finishing her Master's in Nursing this June. As an outpatient department nurse, she is a seasoned nurse in providing health teachings to her patients making her also an excellent study guide writer for student nurses. Marianne is also a mom of a toddler going through the terrible twos and her free time is spent on reading books!

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