What is Phenylketonuria?

It is a rare genetic disease in which the body of an individual is unable to break down Phenylalanine, a type of amino acid. It is abbreviated as PKU.

The condition is also referred to by various other names, such as:

  • Phenylalanine hydroxylase deficiency
  • Idiotica phenylpyruvica
  • Oligophrenia phenylpyruvica
  • Imbecilitas phenylpyruvica
  • Folling’s disease
  • Hyperphenylalaninaemia Type I

Phenylketonuria ICD9 Code

The ICD9 Code for this condition is 270.1.

Phenylketonuria Incidence

The classical form of this disorder manifests in around 1 out of every 15,000 newborns in the United States. The condition has its highest prevalence in Turkey, with one out of every 2,600 children affected by it. It is also common in Northern Ireland, China, Italy and Eastern and Northern Europe.

Phenylketonuria Causes

The condition results from a genetic mutation. The impaired gene responsible for this disorder comprises of instructions for manufacturing an enzyme that is necessary to process the amino acid Phenylalanine.

Aminio acids are responsible for building protein in the human body. In PKU patients, a genetic impairment leads to a partial or complete deficiency of the enzyme responsible for manufacturing protein. In the absence of this enzyme, there can be an accumulation of high levels of Phenylalanine (that are dangerous for the human body) when a sufferer consumes milk, nuts, cheese, meat and other foods that are rich in protein. Eventually, this can result in acute health problems.

A child inherits PKU when both his parents are sufferers of the gene and pass it on to him. Even if either of the parents is not a sufferer, he or she may be a carrier of the impaired gene and not exhibit any symptoms of the disorder at all. PKU is often transmitted to children from parents who are absolutely unaware of being carriers of the defective gene.

Phenylketonuria Types

The disorder is categorized into the following types:

Type I

Also known as Classical PKU, it is inherited in an autosomal recessive manner. The locus of the gene responsible for this disease is present on the long arm of the chromosome 12. This defective gene has more than one allelic form.

Type II

In such cases, there is retention of up to 5% of the activity of the enzymes, as a result of differing phenotypic expression or less severe mutations in the sequence of the enzymes. Type II patients usually suffer less severe symptoms of the disorder that exhibits itself in the later stages of life.

Type III

It is also known as Malignant PKU as a result of deficiency in the metabolism or synthesis of Tetrahydrobiopterin (THB), an enzyme co-factor that is vital for the hydroxylation of Tryptophan and Tyrosine. Type III sufferers are likely to suffer from a more serious type of neurological condition that does not show full response to changes in the diet.

Phenylketonuria Symptoms

In the initial stages, newborn with this disorder do not exhibit any symptoms. However, babies may develop PKU symptoms within a few months in the absence of medical treatment. The problems may be moderate or severe in intensity and may include:

  • Microcephaly or small-sized head
  • Short stature
  • Mental retardation
  • Social or behavioral problems
  • Tremors, seizures, or jerking movements in the limbs
  • Hyperactivity
  • Skin rashes (Eczema)

Affected children may also exhibit a musty odor in their urine, skin or breath, resulting from excessive amounts of phenylalanine in their system. As the body cannot change phenylalanine into melanin (the pigment responsible for hair and skin tone), patients have blue eyes and fair skin.

Children affected by Type I PKU generally suffer from mental retardation that is permanent and fully apparent. Patients of milder forms of the disorder are generally at a lower risk of suffering an extensive brain damage. However, most children with such forms of the condition need a special diet to avoid mental retardation and other complications.

Phenylketonuria Diagnosis

A simple blood test is usually enough to easily detect this disorder. As part of the screening panel for newborns, a PKU screening test is needed by all US states. The exam is usually conducted by drawing a small amount of blood from babies before they are discharged from the hospital. Blood is usually drawn from the arm or the heel of babies with the aid of a lancet or a needle. Blood is tested in laboratories to determine the presence of metabolic disorders, such as PKU. The exam is not conducted until the baby is a day old or before it has consumed some protein to ensure perfect results.

In cases where initial screening test yields positive results, further urine and blood tests may be needed to confirm the diagnosis. Affected infants need to be fed a special formula that can be continued for a lifetime as a rich source of proteins other than Phenylalanine.

Phenylketonuria Differential Diagnosis

During differential diagnosis, the signs of Phenylketonuria should be told apart from similar symptoms arising due to various other conditions like:

  • Various disorder characterized by mental retardation
  • Tyrosinaemia types I and II
  • Type II PKU or HPA
  • THB deficiency or Malignant PKU
  • Any cause of liver disease in children or infants

Phenylketonuria Treatment

Strict adherence to a diet having extremely low amounts of Phenylalanine, mostly present in protein-rich foods, can treat the condition. This is especially necessary when a child is growing up. The diet needs to be followed strictly and needs close supervision by a qualified physician or dietician. Children continuing the diet into adulthood are found to have a better mental and physical health.

Phenylalanine-free Diet

A diet free from Phenylalanine involves absence of such protein rich foods and eatables like:

  • Eggs
  • Milk
  • Nuts
  • Beans
  • Soybeans
  • Fish
  • Beer
  • Peas
  • Chocolate candy
  • Pork
  • Cheese
  • Steaks and other beef products
  • Artificial sweeteners like Nutrasweet (Aspartame)

Infants with PKU should be given Lofenalac, a special infant formula. It contains very low amounts of Phenylalanine and contains a balance of other vital amino acids. It can be used for life as a source of protein.

Use of supplements like fish oil can replace the long-chain fatty acids absent from a standard die free of Phenylalanine. Such products can improve the development of nervous system, including fine motor coordination. Patients may also need other particular supplements like Carnitine or Iron.


The medicine Sapropterin (Kuvan) has been approved by the Food and Drug Administration (FDA) for the treatment of PKU. The drug works by enhancing the tolerance level of sufferers to the amino acid Phenylalanine. The medicine can be used in combination with a low-Phenylalanine diet.

However, the medicine does not work well for all PKU-affected individuals. While FDA has approved the medication, no studies have yet been conducted in determining the effectiveness and long-term safety of Sapropterin.

Phenylketonuria Risk Factors

The risk factors for the disorder are as follows:

Having parents with PKU

Children having both parents as carriers of the gene responsible for the disorder are at risk of developing PKU. As the condition is autosomal recessive, and not a dominant recessive one, patients are at no risk with only of their parents being a sufferer of the disorder.

Belonging to certain regions

Certain populations have also been found to be at greater risk of having the disorder. The defect is mainly found to affect people belonging to the US and Europe. It is rarer in Latinos and Asians. The condition has its lowest incidence in Africa.

Not following PKU diet

Kids with mothers suffering from PKU but not following a special diet during pregnancy, to prevent the complications of the condition, are also highly susceptible to developing this disease. Although such children do not often suffer from PKU, they may develop acute consequences due to the presence of excessive levels of the amino acid Phenylalanine in the bloodstream of their mothers.

Phenylketonuria Complications

In the absence of proper treatment, PKU can cause irreversible damage to the brain and prominent mental retardation within the first few months after birth. In older kids, the condition may be manifested through seizures and behavioral problems. In individuals not adhering to a very low- Phenylalanine diet, Attention-Deficit Hyperacitivity Disorder (ADHD) is found to be the most common problem.

Phenylketonuria Prognosis

If left untreated, the condition can result in progressive worsening of mental capabilities and retarded developmental during childhood and pregnancy. The long-term outcome is very good for those sticking to dietary modifications and taking assistance of medical therapies. The intelligence is normal or close-to- normal, although some affected individuals may suffer from significant challenges while pursuing education in the later years of their life.

Phenylketonuria Life Expectancy

The condition does not shorten the lifespan of patients in any way, even in the absence of treatment, especially if Phenylalanine is avoided when the body and brain is in the developmental stage.

Phenylketonuria and Pregnancy

Women suffering from PKU and becoming pregnant are at risk of suffering from another form of the disease, known as Maternal Phenylketonuria. Women should follow a low- Phenylalanine diet before and after pregnancy to reduce the risk of their fetus developing the condition. Those suffering from PKU should continue such a diet for their life.

Phenylketonuria Prevention

The development or worsening of the condition can be prevented by adapting the following measures:

Undergoing Genetic counseling

People having a family member or a child with the condition, or a personal history of the disorder, may derive benefit from preconception genetic counseling. A geneticist can help guide sufferers better and make them understand how the gene responsible for PKU is passed on from one generation to another of the same family.

Following a low- Phenylalanine diet

Women suffering from the disorder can prevent birth defects in their children by adhering to a diet low in Phenylalanine before they become pregnant. Those with even mild forms of PKU should follow such a diet, to avoid risking the health of their unborn child. Women having a history of the disorder should get in touch with a physician and have a proper discussion before trying to conceive.


If anyone in your family is suffering from PKU, or if your infant has not yet been tested for the disorder, seek medical attention on an immediate basis.


Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.