Dealing with Phenylketonuria (PKU)

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PKU: An Amino Acid Disorder

Amino acid disorders incidence excluding Phenylketonuria (PKU) in West Midland (1 in 5354) according to the study conducted in year (Sanderson et al, 2006). In British Columbia Amino acid disorder in Newborns is 24 in 100,000 births and 1/ 4,200 (Applegarth et al, January 2000)


The occurrence of PKU varies among ethnic groups and geographic regions worldwide.

Local Prevalence

In a study using newborn screening data from West Midlands region of England, PKU prevalence was not found to be significantly different among Pakistani and white children (∼ 0.7/10,000 vs ∼ 0.8/10,000), although the gene frequency was much lower in the Pakistani population (Hutchesson, 1998).

Global Prevalence

Babies in the United States are screened for PKU shortly after birth. The condition is uncommon in this country, only affecting about 1 in 10,000 to 15,000 newborns each year. PKU is more common in individuals with Irish, northern European, Turkish, or Native American ancestry. It is less common in people of African, Japanese, or Ashkenazi Jewish backgrounds.

The incidence of PKU is approximately 1 in 12,000 Caucasians. It is less common in the African-American population, with an incidence of approximately 1 in 50,000 based on newborn screening data from the state of Maryland. PKU is rare in Finland and Japan (National Institutes of Health Consensus Development Panel). The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000 (Pubmed: Hardelid et al. 2008­)

To, approximately 1 in 10,000 or 0.01% or 27,200 people in USA can counteract phenylketonuria. The estimate number per area ratio in Pakistan is 15,919 in 159, 196, 3362 as compared to that of 29,365 in 293, 655, 4051 of USA and 6,027 in 60,270,708 for UK. The following tables have been extrapolated with estimates from the aforementioned prevalence rate:

Phenylketonuria in Southern Asia (Extrapolated Statistics)
Afghanistan 2,851 28,513,6772
Bangladesh 14,134 141,340,4762
Bhutan 218 2,185,5692
India 106,507 1,065,070,6072
Pakistan 15,919 159,196,3362
Sri Lanka 1,990 19,905,1652


Phenylketonuria in North America (Extrapolated Statistics)
USA 29,365 293,655,4051
Canada 3,250 32,507,8742
Mexico 10,495 104,959,5942


Phenylketonuria in Western Europe (Extrapolated Statistics)
Britain (United Kingdom) 6,027 60,270,708 for UK2
Belgium 1,034 10,348,2762
France 6,042 60,424,2132
Ireland 396 3,969,5582
Luxembourg 46 462,6902
Monaco 3 32,2702
Netherlands (Holland) 1,631 16,318,1992
United Kingdom 6,027 60,270,7082
Wales 291 2,918,0002


Phenylketonuria in Eastern Asia (Extrapolated Statistics)
China 129,884 1,298,847,6242
Hong Kong s.a.r. 685 6,855,1252
Japan 12,733 127,333,0022
Macau s.a.r. 44 445,2862
North Korea 2,269 22,697,5532
South Korea 4,823 48,233,7602
Taiwan 2,274 22,749,8382


What is Phenylketonuria?

Historically, newborn screening originated with Dr. Robert Guthrie who developed a test for elevated phenylalanine (PKU) in dried blood spots. Other names of which are: Phenylalanine Hydroxylase (PAH) Deficiency Disease, Neonatal Phenylketonuria and Folling’s Disease

Types and Symptoms

The severe signs and symptoms of PKU are rare in the US, as early screening allows treatment to begin soon after birth.

PKU symptoms can range from mild to severe. The most severe form of this disorder is known as Classic PKU or Hyperphenylalaninemia.

Classic PKU:

The most severe form of the disorder occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.

An infant with classic PKU may appear normal for the first few months of their life. If the baby isn’t treated for PKU during this time, they’ll start to develop the following symptoms:

  • seizures
  • tremors, or trembling and shaking
  • stunted growth
  • hyperactivity
  • skin conditions, such as eczema
  • a musty odor of their breath, skin, or urine

Variant PKU:

A less severe form of PKU is called variant PKU or non-PKU hyperphenylalaninemia. This occurs when the baby has too much phenylalanine in their body. Infants with this form of the disorder may have only mild symptoms, but they’ll need to follow a special diet to prevent intellectual disabilities.

If PKU isn’t diagnosed at birth and treatment isn’t started quickly, the disorder can cause:

  • irreversible brain damage and intellectual disabilities within the first few months of life
  • behavioral problems and seizures in older children

Once a specific diet and other necessary treatments are started, symptoms start to diminish. People with PKU who properly manage their diet usually don’t show any symptoms.

Mothers and Pregnancy:

Babies born to mothers with PKU and uncontrolled phenylalanine levels (women who no longer follow a low-phenylalanine diet) have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth. These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems. Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

Is Prevention Possible Before Pregnancy?

PKU is a genetic condition, so it can’t be prevented. However, an enzyme assay can be done for people who plan on having children. An enzyme assay is a blood test that can determine whether someone carries the defective gene that causes PKU. The test may also be done during pregnancy to screen unborn babies for PKU.

  • Chorionic villus sampling or amniocentesis can be done during pregnancy to screen the unborn baby for PKU.

Expected Outcomes of PKU Pregnancy:

Woman with PKU may be at risk of complications, including miscarriage, if they don’t follow a PKU meal plan during their child-bearing years. There’s also a chance that the unborn baby will be exposed to high levels of phenylalanine. This can lead to various problems in the baby, including:

  • intellectual disabilities
  • heart defects
  • delayed growth
  • low birth weight
  • an abnormally small head

These signs aren’t immediately noticeable in a newborn, but a doctor will perform tests to check for signs of any medical concerns your child may have.

Cause and Genetic Basis

Cause: The Mutation in PAH gene:

PKU is an inherited condition caused by a defect in the PAH gene. The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase, the enzyme responsible for breaking down phenylalanine. This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet – when someone eats high-protein foods, such as eggs and meat – is not processed effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.

Changes in other genes may influence the severity of PKU, but little is known about these additional genetic factors.

Note: Call your health care provider if your infant has not been tested for PKU. This is particularly important if anyone in your family has the disorder.

Pattern of Inheritance:

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Both parents must pass on a defective version of the PAH gene for their child to inherit the disorder. If just one parent passes on an altered gene, the child won’t have any symptoms, but they’ll be a carrier of the gene.

Testing and Follow-Up

The Newborn Screening

Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.

Since the 1960s, hospitals in the United States have routinely screened newborns for PKU by taking a blood sample. A doctor uses a needle or lancet to take a few drops of blood from your baby’s heel to test for PKU and other genetic disorders.

The screening test is performed when the baby is one to two days old and still in the hospital. If you don’t deliver your baby in a hospital, you’ll need to schedule the screening test with your doctor.


If a child or adult shows symptoms of PKU, such as developmental delays, the doctor will order a blood test to confirm the diagnosis.

Follow-up testing will involve checking your baby’s urine and blood samples for harmful levels of acids and toxins. Certain acids and toxins build up in the body when a child has an amino acid condition, so measuring the levels of these substances in your baby’s body can help doctors determine if your baby has a condition. High amounts phenylalanine in the blood might indicate that your baby has PKU. This test involves taking a sample of blood and analyzing it for the presence of the enzyme needed to break down phenylalanine.

Confirmatory Tests

The PAA (Plasma Amino Acid), urine and/or blood or CSF neopterin and biopterin tests are carried out at AGHA KHAN, AFIP.

For more information, email at


 People with PKU can relieve their symptoms and prevent complications by following a special diet and by taking medications.


The main way to treat PKU is to eat a special diet that limits foods containing phenylalanine. Infants with PKU may be fed breast milk. They usually also need to consume a special formula called as Lofenalac. When your baby is old enough to eat solid foods, you need to avoid letting them eat foods high in protein. These foods include:

  • eggs
  • cheese
  • nuts
  • milk
  • beans
  • chicken
  • beef
  • pork
  • fish

NOTE: The artificial sweetener NutraSweet (aspartame) also contains phenylalanine. Any products containing aspartame should be avoided.

To make sure that they still receive an adequate amount of protein, children with PKU need to consume PKU formula. It contains all the amino acids that the body needs, except for phenylalanine. There are also certain low-protein, PKU-friendly foods that can be found at specialty health stores.

People with PKU will have to follow these dietary restrictions and consume PKU formula throughout their lives to manage their symptoms. It’s important to note that PKU meal plans vary person to person. People with PKU need to work closely with a doctor or dietitian to maintain a proper balance of nutrients while limiting their intake of phenylalanine. They also have to monitor their phenylalanine levels by keeping records of the amount of phenylalanine in the foods they eat throughout the day.

Some state legislatures have enacted bills that provide some insurance coverage for the foods and formulas necessary to treat PKU. Check with your state legislature and medical insurance company to find out if this coverage is available for you. If you don’t have medical insurance, you can check with your local health departments to see what options are available to help you afford PKU formula.

Diet of Older Children and Adults with PKU:

Older children and adults continue to drink or eat a protein substitute formula daily, as directed by a doctor or dietitian. Their daily dose of formula is divided between your meals and snacks, instead of consumed all at once. The formula for older children and adults is not the same as the one used for infants, but it works on the same principle. It acts as an essential nutritional substitute and is continued for life.

Medication and Supplements

  • The United States Food and Drug Administration (FDA) recently approved sapropterin (Kuvan) for the treatment of PKU. Sapropterin helps lower phenylalanine levels. This medication must be used in combination with a special PKU meal plan. However, it doesn’t work for everyone with PKU. It’s most effective in children with mild cases of PKU. For more information please the contact the following.
    • BioMarin Pharmaceutical Inc. Susan Berg Corporate Communications., no. (415) 506-6594


BioMarin Pharmaceutical Inc. 105 Digital Drive Novato, CA 94949. Tel: 415.506.6700, Fax: 415.382.7889

BioMarin has initiated an expanded access program for Kuvan in the U.S. Anyone interested in learning more about this program should speak with their physician or call (877) 811-7327.

  • Taking supplements such as fish oil to replace the long chain fatty acids missing from a standard phenylalanine-free diet may help improve neurologic development, including fine motor coordination. Other specific supplements, such as iron or carnitine, may also be needed.

Medicine for Future Perspective:

As your baby gets older, their doctor may prescribe a medication that contains BH4. BH4 is a substance naturally produced by the body, but your baby’s body might not make enough of it. Taking BH4 supplements may help break down the phenylalanine that builds up. Your baby’s doctor will need to write a prescription for these supplements. BH4 does not work in everyone with PKU. A trial period on the drug with evaluation by a physician is necessary.

Older children and adults use a different formula that provides protein in the amounts they need. People with PKU need to take formula every day for their entire life.

Expected Outcomes

  • If babies start treatment several weeks after birth, some signs of PKU can be avoided.
  • If treatment is started after six months of age, babies are at risk for severe intellectual disabilities.
  • It is important to treat PKU, even if treatment is started after noticing signs and symptoms, in order to help prevent permanent brain damage. School functioning may be mildly impaired.
  • If proteins containing phenylalanine are not avoided, PKU can lead to mental disability by the end of the first year of life.
  • Severe mental disability occurs if the disorder is untreated. ADHD (attention-deficit hyperactivity disorder) appears to be a common problem in those who do not stick to a very low-phenylalanine diet.






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