According to a study, the prevalence of phenylketonuria or PKU is approximately 1 in 18,300 live births. It is a rare genetic disease affecting phenylalanine metabolism, an essential amino acid found in protein. Generally, PKU is a genetically inherited condition that requires special dietary management. 

Thus, apart from people affected by this condition, it is also essential for medical students and practitioners to know about this condition. It will aid them in covering their syllabus and future diagnoses, leading to better outcomes.  

This article covers an overview of phenylketonuria, including what causes it, how it’s diagnosed, and how people live with it. Read on!

What is Phenylketonuria?

Phenylketonuria (PKU) is an autosomal recessive disorder caused by phenylalanine hydroxylase (PAH) gene mutations. Here is an overview of how this condition occurs:

• Usually, this gene helps create an enzyme that facilitates the breakdown of phenylalanine (an amino acid). 
• When this disorder occurs, there is a deficiency in this enzyme, leading to a buildup of phenylalanine in the body. 
• Now, this amino acid can be present in food items that contain protein and aspartame (an artificial sweetener). 

As the body is unable to process the amino acid ingested via the diet, it leads to a buildup in the blood and tissues, leading to phenylketonuria symptoms and cognitive development challenges. 

Following are some additional details on this disorder:

• PKU is the most common inherited defect of amino acid metabolism, resulting in elevated serum phenylalanine concentrations. 
• Different types of PKU are determined by the amount of the enzyme deficient and the degree of phenylalanine levels. 
• These forms range from classic PKU to moderate PKU to mild PKU and benign hyperphenylalaninemia. 
• Classic PKU, the most severe form of the disease, has substantially increased levels of phenylalanine, which, if not treated, can result in severe intellectual disability.

What are the Causes of Phenylketonuria? 

Mutations in both copies of the PAH gene are the most common cause of phenylketonuria. Traits caused by these mutations are inherited when both parents carry the mutated gene as carriers. 

The inheritance pattern is autosomal recessive, meaning a child must inherit the mutated gene from both parents to manifest the disorder. Those with a mutated gene are typically healthy but can pass the mutation down to their children.

Find a comprehensive overview of the phenylketonuria causes below:

Genetic Mutations

The mutations within the PAH gene can be very different from one another and result in varying levels of enzyme function. Some mutations lead to a complete loss of enzymatic activity, while others lead to less active enzyme forms. Generally, in severe cases, there is a significant deficiency of enzymes.

Environmental Factors

PKU is only caused by a genetic mutation, so environmental factors do not result in this disorder. However, having a high-phenylalanine diet can worsen the condition. Individuals affected by this disorder should consider opting for a low-phenylalanine diet.

What are the Risk Factors of Phenylketonuria?

The most common risk factor for PKU is its genetic inheritance: 

Family History

Having a family history of PKU markedly heightens the risk for children. Genetic counselling professionals can assist families in understanding their risk and determining whether they want to pursue genetic testing or make certain choices about family planning.

Ethnic Prevalence

The high frequency of PKU among certain ethnic groups can be attributed to a genetic founder effect. For instance, it is more frequent in individuals of European descent than those of African or Asian descent.

What are the Symptoms of Phenylketonuria?

The symptoms of phenylketonuria do not appear immediately after birth but are gradually visible with the increase in phenylalanine level. In this regard:

• Untreated PKU results in moderate to severe neurological symptoms. They range from developmental delays to intellectual disability to seizures and behavioural problems. This brain toxicity happens because of elevated phenylalanine levels. 
• It also leads to physical symptoms, including lighter skin, hair, and eye colour from reduced melanin production. 
• Additional symptoms are eczema, a musty body odour, and tremors. 

These complications can be prevented with early diagnosis and treatment.

How to Diagnose Phenylketonuria Condition?

PKU is diagnosed shortly after birth through a series of newborn screening tests to assess blood levels of phenylalanine. In many countries, these tests are standard practice in the first few days of life. 

If phenylalanine levels are found to be high on the preliminary results, additional testing is performed to confirm the diagnosis and provide information about the severity of the disorder. Find a detailed overview below:

Newborn Screening

Diagnosis of PKU Newborn screening for phenylketonuria involves a blood test for phenylalanine through a heel prick. It is an essential test for preventable detection and intervention.

Confirmatory Testing

A confirmation test will be performed when newborn screening demonstrates an increased phenylalanine level. This may involve genetic testing to look for mutations in the PAH gene and further blood tests to check for enzyme activity.

What are the Treatment Options for Phenylketonuria?

The treatment for PKU includes a low-phenylalanine diet and other factors, which are essential for preventing intellectual disability and associated issues: 

Dietary Management

A low-phenylalanine diet is the foundation of PKU treatment. This diet limits foods containing large amounts of phenylalanine, including meat, fish, eggs, dairy products, and certain grains. Low phenylalanine intake is balanced by specialised formulas/supplements to meet individual nutrition requirements across the patient’s lifespan.

Medications

Certain medications, such as sapropterin dihydrochloride, can help control PKU by enhancing the function of the phenylalanine hydroxylase enzyme. However, these drugs do not work for everyone and are usually prescribed along with dietary restrictions.

Lifestyle Adjustments

Due to high levels of phenylalanine, people with PKU are encouraged to eliminate certain foods from their diet to prevent serious complications. This involves strictly monitoring phenylalanine levels in their diet and repeated blood tests to ensure sufficient compliance and maintenance of levels within target ranges.

Although newer medications may enable some people to be less restrictive with their eating habits, the diet must be strictly controlled for life. 

FAQs About Phenylketonuria Condition

1. What are the symptoms of phenylketonuria?

Phenylketonuria symptoms include intellectual disability, developmental delays, seizures, hyperactivity, and a musty odour in breath or urine. Babies may appear normal at birth but develop symptoms within months if untreated. Other signs include skin rashes, light skin and hair due to melanin deficiency, and behavioural issues.

2. What is the main cause of phenylketonuria?

PKU is caused by a genetic mutation in the PAH gene, responsible for producing phenylalanine hydroxylase. This enzyme breaks down phenylalanine, an amino acid found in protein-rich foods. When the enzyme is deficient or absent, phenylalanine accumulates in the blood, leading to brain damage and neurological issues.

3. What happens when you have phenylketonuria?

Without proper management, PKU leads to a toxic buildup of phenylalanine, affecting brain development. This results in intellectual disability, seizures, and behavioural issues. A strict low-phenylalanine diet is crucial to prevent complications. If treated early, individuals with PKU can lead normal, healthy lives with dietary and medical supervision.

4. How is phenylketonuria diagnosed?

PKU is diagnosed through newborn screening, typically a heel-prick blood test within the first few days of life. The test measures phenylalanine levels in the blood. If levels are high, further genetic testing or enzyme analysis confirms the diagnosis. Early detection is essential for timely dietary management to prevent complications.

5. What is the cause of phenylketonuria deficiency?

PKU deficiency results from mutations in the PAH gene, leading to a lack of phenylalanine hydroxylase enzyme. This enzyme is necessary to break down phenylalanine, and its deficiency causes the amino acid to accumulate in the blood, resulting in toxic effects on the brain and nervous system if left untreated.

Conclusion

Understanding phenylketonuria symptoms, causes, and treatment options is essential for individuals and families affected by this condition. People with PKU can lead healthy and fulfilling lives by recognising the importance of dietary restrictions and medical interventions. Early detection and proper management can significantly improve outcomes for those with PKU, emphasising the importance of newborn screening and ongoing care. 

For those interested in learning more about genetic disorders and their management, DocTutorials offers comprehensive educational materials, including top-quality video lectures, mock tests, revision programmes, and study aids for medical students and professionals. Check out our NEET PG courses today and take another step towards your dream medical career!