Author: Daniela Berardi
Date: 12/11/2007



Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. Amino acids are the building blocks for body proteins. Essential amino acids can only be obtained from the food we eat as our body does not normally produce them. In 'classic PKU', the enzyme that breaks down phenylalanine phenylalanine hydroxylase, is completely or nearly completely deficient. This enzyme normally converts phenylalanine to another amino acid, tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes, accumulate in the blood and body tissues. Although the term hyperphenylalaninemia strictly means elevated blood phenylalanine, it is usually used to describe a group of disorders other than classic PKU. These other disorders may be caused by a partial deficiency of the phenylalanine breakdown enzyme or the lack of another enzyme important to the processing of this amino acid. A normal blood phenylalanine level is about 1 mg/dl. In classic PKU, levels may range from 6 to 80mg/dl, but are usually greater than 30mg/dl. Levels are somewhat less in the other disorders of hyperphenylalaninemia. Chronically high levels of phenylalanine and some of its breakdown products can cause significant brain problems. Classic PKU is the most common cause of high levels of phenylalanine in the blood and will be the primary focus of this topic sheet.


Classic PKU and the other causes of hyperphenylalaninemia affect about one of every 10,000 to 20,000 Caucasian or Oriental births. The incidence in African Americans is far less. These disorders are equally frequent in males and females.


PKU and the other causes of hyperphenylalaninemia are inherited in a recessive fashion. This means an affected person inherited two traits for the disorder (e.s., one from each parent). A person with one trait for the disorder, is called a 'carrier' for PKU. Carriers do not have symptoms of the disorder.


Infants with PKU appear normal at birth. Many have blue eyes and fairer hair and skin than other family members. Currently, most symptoms of untreated PKU are avoided by newborn screening, early identification, and management.

The following describes untreated PKU symptoms-currently a rarity:

About 50% of untreated infants have early symptoms, such as vomiting, irritability, an eczema-like rash, and a mousy odor to the urine. Some may also have subtle signs of nervous system function problems, such as increased muscle tone, and more active muscle tendon reflexes. Later, severe brain problems occur, such as mental retardation and seizures. Other commonly noted features in untreated children include: microcephaly (small head), prominent cheek and upper jaw bones with widely spaced teeth, poor development of tooth enamel, and decreased body growth.


Every state now screens the blood phenylalanine level of all newborns at about 3 days of age. This test is one of several newborn screening tests performed before or soon after discharge from the hospital. Usually, a few drops of blood are obtained by a small prick on the heel, placed on a card, and then sent for measurement. If the screening test is abnormal, other tests are needed to confirm or exclude PKU. Newborn screening allows early identification and early implementation of treatment.

The goal of PKU treatment is to maintain the blood level of phenylalanine between 2 and 10 mg/dl. Some phenylalanine is needed for normal growth. This requires a diet that has some phenylalanine but in much lower amounts than normal. High protein foods, such as: meat, fish, poultry, eggs, cheese, milk, dried beans, and peas are avoided. Instead, measured amounts of cereals, starches, fruits, and vegetables, along with a milk substitute are usually recommended. Phenylalanine free formulas are available for all age groups. In some clinics, a phenylalanine 'challenge' may be suggested to evaluate whether or not the child continues to require a low phenylalanine diet. This test identifies those few persons with a transient or 'variant' form of the disorder. However, most authorities currently recommend lifelong dietary restriction of phenylalanine for individuals with classic PKU, in order to promote maximal development and cognitive abilities. Trying to reinstitute the PKU diet after a period of 'relaxation' to a regular diet, has been difficult for many individuals. Periodic phenylalanine blood level measurement, and the guidance of a nutritionist and other members of the health care team, allow individuals and families to work toward consistently maintaining the blood level in the desirable range. Fever and illness can cause normal body proteins to break down, the liberation of the body's own amino acids, and thus, a rise of the blood phenylalainine level. The physician and nutritionist can suggest dietary changes to help maintain levels in the desirable range during illness. Medical follow-up often involves periodic developmental screening. This checks for the expected normal development over time, and allows early recognition and intervention for problems.

Berardi Daniela (matr. 300429) e Coppo Alessandra (matr. 276329 27)
Scuola di Specializzazione in Patologia Clinica 2° Anno

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