Phenylketonuria (PKU) is a rare genetic disorder that affects the way the body processes an amino acid called phenylalanine. Phenylalanine is one of the building blocks of proteins and is found in many foods, especially those that contain protein or aspartame, an artificial sweetener. Normally, an enzyme called phenylalanine hydroxylase (PAH) breaks down excess phenylalanine in the body and converts it into another amino acid called tyrosine. However, in people with PKU, the PAH gene is mutated and the enzyme is either missing or not working properly. This leads to a buildup of phenylalanine in the blood and brain, which can cause serious health problems.
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Types and Symptoms of PKU
There are two main types of PKU: classic PKU and variant PKU. Classic PKU is the most severe form of the disorder, where the PAH enzyme is completely absent or has very low activity. People with classic PKU have very high levels of phenylalanine in their blood and need to follow a strict low-phenylalanine diet to prevent brain damage and intellectual disability. Variant PKU is a milder form of the disorder, where the PAH enzyme has some residual activity and can break down some phenylalanine. People with variant PKU have lower levels of phenylalanine in their blood and may need a less restrictive diet or medication to control their condition.
The symptoms of PKU vary depending on the type and severity of the disorder, as well as the treatment and diet adherence. If left untreated, PKU can cause:
– A musty odor in the breath, skin or urine, caused by too much phenylalanine in the body
– Nervous system problems that may include seizures, tremors, hyperactivity, attention deficit disorder, anxiety, depression, and psychosis
– Skin rashes, such as eczema
– Lighter skin, hair and eye color than family members, because phenylalanine can’t transform into melanin — the pigment responsible for hair and skin tone
– Unusually small head size (microcephaly)
– Intellectual disability
– Delayed development
– Behavioral, emotional and social problems
If treated early and consistently, most people with PKU can lead normal and healthy lives. However, they still need to monitor their blood phenylalanine levels regularly and follow a special diet throughout their lives.
Diagnosis and Treatment of PKU
PKU is diagnosed through newborn screening programs in many countries. A blood sample is taken from the baby’s heel shortly after birth and tested for phenylalanine levels. If the levels are abnormally high, further tests are done to confirm the diagnosis and determine the type of PKU. Genetic testing can also identify carriers of the mutated PAH gene.
The main treatment for PKU is a diet that limits foods that contain phenylalanine. These include meat, fish, eggs, dairy products, nuts, beans, soy products, breads, cereals, pasta, chocolate, and aspartame-sweetened foods and drinks. Instead, people with PKU need to eat foods that are low in phenylalanine or specially made for them. These include fruits, vegetables, some grains, special formulas or supplements that provide essential nutrients without phenylalanine.
The amount of phenylalanine that a person with PKU can tolerate depends on their age, weight, activity level, type of PKU, and individual response to treatment. A dietitian can help plan a suitable diet for each person with PKU based on their blood phenylalanine levels and nutritional needs.
Some people with PKU may also benefit from medication that helps lower their blood phenylalanine levels or increase their PAH enzyme activity. These include:
– Sapropterin dihydrochloride (Kuvan), a synthetic form of a natural cofactor that helps the PAH enzyme work better. It can be taken as a tablet or dissolved in water once a day.
– Pegvaliase (Palynziq), an injectable form of an enzyme that breaks down phenylalanine into harmless byproducts. It can be given as a subcutaneous injection once or twice a day.
These medications are not effective for everyone with PKU and may have side effects such as headache, nausea, diarrhea, rash, injection site reactions, allergic reactions, or joint pain. They also do not replace the need for a low-phenylalanine diet.
Complications and Prognosis of PKU
If untreated or poorly managed, PKU can cause irreversible brain damage and intellectual disability. It can also affect other organs such as the heart, liver, kidneys, bones, and skin. People with PKU are also at risk of developing other health problems such as:
– Osteoporosis, a condition that causes weak and brittle bones
– Dental problems, such as tooth decay and gum disease
– Anemia, a condition that causes low red blood cell count and fatigue
– Eye problems, such as cataracts and glaucoma
– Neurological problems, such as headaches, migraines, and nerve damage
Women with PKU who become pregnant need to be especially careful about their diet and blood phenylalanine levels. High levels of phenylalanine can cross the placenta and harm the developing baby. This can cause a condition called maternal PKU syndrome, which can result in:
– Heart defects
– Low birth weight
– Small head size
– Intellectual disability
– Miscarriage or stillbirth
To prevent these complications, women with PKU should follow a strict low-phenylalanine diet before and during pregnancy. They should also take prenatal vitamins and folic acid supplements to support their baby’s growth and development.
The prognosis of PKU depends on the type and severity of the disorder, the age of diagnosis, the adherence to treatment and diet, and the availability of medical care and support. With early diagnosis and lifelong treatment, most people with PKU can have normal intelligence, health, and life span. However, they still need to cope with the challenges of following a special diet and taking medication for the rest of their lives.
Conclusion
Phenylketonuria is a rare genetic disorder that causes abnormal metabolism of phenylalanine, an amino acid found in many foods. It can lead to serious health problems if left untreated or poorly managed. The main treatment for PKU is a diet that limits foods that contain phenylalanine and includes special supplements or formulas. Some people with PKU may also benefit from medication that helps lower their blood phenylalanine levels or increase their PAH enzyme activity. People with PKU need to monitor their blood phenylalanine levels regularly and follow a special diet throughout their lives. Women with PKU who become pregnant need to be especially careful about their diet and blood phenylalanine levels to prevent harm to their babies. With early diagnosis and lifelong treatment, most people with PKU can lead normal and healthy lives.
