Phenylketonuria: Causes and Types

September 7, 2023

Phenylketonuria: Causes and Types
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What is Phenylketonuria?

An uncommon genetic condition called phenylketonuria (PKU) results in a hazardous accumulation of the amino acid phenylalanine in the body. The phenylalanine hydroxylase (PAH) gene, which contributes to the generation of the enzyme needed to break down phenylalanine, is the gene responsible for PKU. A dangerous accumulation can occur when a person with PKU consumes protein-containing foods or aspartame, an artificial sweetener, because this person lacks the enzyme required to break down phenylalanine.  PKU can cause serious health problems such as intellectual incapacity, convulsions, and behavioral issues. A low-phenylalanine diet, medication, and ongoing monitoring are all part of the treatment.

  • What is Phenylketonuria?
  • Types of Phenylketonuria
  • Causes of Phenylketonuria
  • Symptoms of Phenylketonuria
  • Diagnosis of Phenylketonuria
  • Treatment of Phenylketonuria
  • Conclusion
  • Frequently Asked Questions

Types of Phenylketonuria

The main determinants of the various forms of phenylketonuria (PKU) are the severity of the illness and the amount of remaining enzymatic activity. The following are the main forms of PKU:

  1. Classic PKU: This is the most severe form of PKU and is characterized by a considerable lack of phenylalanine hydroxylase (PAH) activity. A low-phenylalanine diet must be closely followed by those with classic PKU in order to avoid intellectual impairments and other health problems.
  2. Variant PKU: When compared to conventional PKU, this variant retains some PAH enzyme activity. Variant PKU sufferers may still need to restrict their consumption of phenylalanine, but frequently to a smaller extent than those with classic PKU.
  3. Non PKU Hyperphenylalaninemia refers to conditions with increased phenylalanine levels that do not meet the diagnostic cutoff for classic or variant PKU. Monitoring and dietary management are still crucial to avoid potential cognitive and neurological problems, even though the course of treatment might not be as strict as in classic PKU.

These variations in PKU types aid in identifying the degree of dietary management necessary and the potential health outcomes for those who have the condition. To reduce the dangers, early diagnosis and adequate treatment are crucial.

Causes of Phenylketonuria

The phenylalanine hydroxylase (PAH) gene mutations are the main genetic causes of phenylketonuria (PKU). An enzyme termed phenylalanine hydroxylase, which is created in response to instructions from the PAH gene, breaks down the amino acid phenylalanine.  Patients with PKU are unable to adequately metabolize phenylalanine because mutations in the PAH gene result in a deficit or absence of this enzyme.

The main causes of PKU are as follows:

1. Genetic Inheritance

PKU often has an autosomal recessive inheritance type. This means that for a child to get PKU, both of its parents must have a mutant PAH gene.

2. PAH Gene Mutations

The severity of PKU might vary depending on which of the many potential mutations in the PAH gene an individual inherits.

3. Inherited Metabolic Disorder

Due to irregularities in the body’s metabolic processes, particularly in the metabolism of phenylalanine, PKU is regarded as an inherited metabolic illness.

For the diagnosis and treatment of PKU, it is crucial to comprehend the genetic phenylketonuria that causes mutations in the PAH gene. Early detection and treatment, frequently accomplished through newborn screening, can aid in averting related health issues.

Symptoms of Phenylketonuria

Phenylketonuria (PKU) symptoms can range from moderate to severe and might include:

  1. Too much phenylalanine in the body can create a musty smell that appears in the breath, skin, or urine.
  2. Seizures are among the neurological (nervous system) issues that might occur.
  3. Skin conditions like eczema
  4. Compared to family members, they have lighter skin, hair, and eyes because phenylalanine cannot produce melanin.
  5. (Microcephaly) A very small head size
  6. Hyperactivity
  7. Behavioral issues, including repeated tantrums and self-harming incidents
  8. Delays in development
  9. Impairments of the intellect
  10. Seizures 

Untreated PKU symptoms, which can range from mild to severe, can cause irreparable brain damage, intellectual disability, neurological issues,  emotional and social issues in older kids and adults, as well as serious health and developmental issues. PKU can be identified with a blood test.

Diagnosis of Phenylketonuria

Phenylketonuria (PKU) is virtually always detected during newborn screening. In all 50 states in the US, babies must undergo PKU screening. Infants are routinely screened for PKU in many other nations as well.

Blood tests: As part of standard newborn screening, healthcare professionals use blood tests to confirm a diagnosis of PKU quickly. Your doctor will perform more testing, typically more blood or urine tests, to confirm the diagnosis and the kind of PKU if your kid has high phenylalanine levels in their blood sample.

Hereditary testing: Because PKU is a hereditary disorder, a genetic test can identify the particular mutation that is causing symptoms.

Treatment of Phenylketonuria

PKU is a chronic disorder that requires ongoing monitoring and a low-phenylalanine diet.

Low-phenylalanine diet

PKU patients must adhere to a diet that restricts phenylalanine-containing foods. The diet should be properly followed and begun as soon as possible after delivery. Each person has a different safe intake level of phenylalanine. As a result, a PKU patient needs to design an individualized diet in collaboration with a healthcare provider. 

The idea is to consume no more phenylalanine than is required for normal growth and bodily functions. For the purpose of assessing how well the diet is working, frequent blood tests and medical visits are required.

Regular monitoring

Your PKU diagnosis is permanent, so keep in touch with your doctor and have regular blood tests to check your body’s phenylalanine levels. You still need to eat meals and take vitamins if you’re on a limited diet to make up for the lack of protein. Make sure to adhere to your diet for the rest of your life to avoid any potential symptoms.

PKU is diagnosed through neonatal screening, blood tests, and genetic analysis. A low-phenylalanine diet, medication, and routine monitoring are all used to treat PKU. The low-phenylalanine diet needs to be carefully followed and should begin as soon as the baby is born. Each person has a different safe intake level of phenylalanine. 

As a result, a PKU patient needs to design an individualized diet in collaboration with a healthcare provider. The idea is to consume no more phenylalanine than is required for normal growth and bodily functions. For the purpose of assessing how well the diet is working, frequent blood tests and medical visits are required.


Depending on the severity of the ailment, phenylketonuria (PKU), a metabolic disorder with genetic roots, may have varied effects on different people. To properly treat and assist those who have PKU, it is essential to comprehend the many causes and kinds of the condition. While PKU is typically an inherited condition, exploring the potential for phenylketonuria causes can shed light on preventive measures and therapies. Effective treatment of PKU requires early diagnosis, a specialized diet, and continued medical care. We can improve the quality of life for people with PKU and encourage more study into the condition’s underlying causes by increasing public awareness of these issues.

Frequently Asked Questions

1. What is the Main Cause of Phenylketonuria?

Genetic abnormalities in the PAH gene mostly cause phenylketonuria (PKU). As a result of these mutations, the phenylalanine hydroxylase enzyme is deficient, preventing normal phenylalanine breakdown. PKU normally has an autosomal recessive inheritance pattern, which means both parents must have a gene mutation for a kid to be affected.

2. Is Phenylketonuria an Enzyme Disorder?

The enzyme disorder, phenylketonuria (PKU), is real. Lack of the phenylalanine hydroxylase enzyme is the result of mutations in the PAH gene. The amino acid phenylalanine must be broken down in order for this enzyme to function. In PKU, the lack of the enzyme causes a buildup of phenylalanine in the blood, which can cause health problems if not carefully controlled through dietary restrictions.

3. What Happens in Phenylketonuria?

Because of a lack of the phenylalanine hydroxylase enzyme in people with phenylketonuria (PKU), the body is unable to metabolize the amino acid phenylalanine effectively. Phenylalanine builds up in the blood as a result, possibly resulting in cognitive and neurological problems. To avoid these problems, early diagnosis and nutritional control are essential.

Disclaimer: We recommend consulting a Doctor before taking any action based on the above shared information.



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