How is Phenylketonuria diagnosed?

Diagnosis of Phenylketonuria (PKU)

Phenylketonuria (PKU) is a genetic disorder that affects the body's ability to break down an amino acid called phenylalanine. If left untreated, high levels of phenylalanine can build up in the blood and cause various health problems, including intellectual disability and other neurological issues. Early diagnosis of PKU is crucial to prevent these complications and initiate appropriate treatment.

1. Newborn Screening

Newborn screening is the primary method used to diagnose PKU. It is a routine test performed shortly after birth to identify several genetic disorders, including PKU. A few drops of blood are collected from the baby's heel and sent to a laboratory for analysis.

The blood sample is tested for the levels of phenylalanine. If the phenylalanine levels are elevated, it may indicate the presence of PKU. However, it is important to note that a single elevated phenylalanine level does not confirm the diagnosis of PKU. Further testing is required to confirm the condition.

2. Confirmatory Testing

If the initial newborn screening suggests elevated phenylalanine levels, additional tests are performed to confirm the diagnosis of PKU. These tests may include:

• Blood Test: A blood sample is taken to measure the levels of phenylalanine and other amino acids. Elevated phenylalanine levels and decreased levels of other amino acids are characteristic of PKU.


• Genetic Testing: Genetic testing is conducted to identify mutations in the gene responsible for PKU, known as the phenylalanine hydroxylase (PAH) gene. This test helps confirm the diagnosis and determine the specific genetic mutation causing PKU.

3. Differential Diagnosis

During the diagnostic process, it is essential to rule out other conditions that may present with similar symptoms to PKU. Some conditions that may be considered in the differential diagnosis include:

• Transient Hyperphenylalaninemia: This condition causes temporary elevation of phenylalanine levels in newborns but resolves on its own without causing long-term complications.


• Maternal PKU: In rare cases, a pregnant woman with PKU can pass on phenylalanine to the developing fetus, leading to intellectual disability and other complications. Maternal PKU requires specific management during pregnancy.


• Other Metabolic Disorders: Some metabolic disorders, such as tyrosinemia or maple syrup urine disease, may also present with elevated phenylalanine levels. Differential diagnosis helps differentiate PKU from these conditions.

4. Clinical Evaluation

In addition to laboratory tests, a thorough clinical evaluation is essential in diagnosing PKU. This evaluation involves:

• Medical History: Gathering information about the patient's symptoms, family history, and any previous newborn screening results.


• Physical Examination: A physical examination may reveal certain physical features associated with PKU, such as fair skin, light hair, and blue eyes.


• Neurological Assessment: Assessing the patient's neurological development and cognitive abilities is crucial in diagnosing PKU, as it is primarily a neurological disorder.

Once the diagnosis of PKU is confirmed, appropriate treatment and management strategies can be initiated. Early intervention is crucial to prevent the complications associated with PKU and promote optimal development and quality of life for individuals with the condition.