Phenylketonuria (PKU)

Phenylketonuria (PKU) is an inborn error in phenylalanine metabolism that results in the accumulation of high serum levels of the enzyme phenylalanine in the blood. When left untreated, it results in cerebral damage and mental retardation.

Causes

A mutation in a single gene causes PKU. This gene contains the instructions for making an enzyme needed to process the amino acid called phenylalanine. Amino acids are the building blocks for protein. In a person with PKU, this gene is defective, causing a complete or near-complete deficiency of the enzyme. Without the enzyme necessary to process phenylalanine, a dangerous buildup of this amino acid can develop when a person with PKU eats foods that are high in protein, such as milk, cheese, nuts or meats. This can eventually lead to serious health problems.

For a child to inherit PKU, both the mother and father must have and pass on the defective gene. This pattern of inheritance is called autosomal recessive. A parent can have the defective gene, but not have the disease. This is called being a "carrier." Most often, PKU is passed down the family tree by parents who are carriers of the disorder but don't know it.

Signs and symptoms

An infant with undiagnosed and untreated PKU appears normal at birth but by 4 months begins to show signs of arrested brain development, including mental retardation and, later, personality disturbances (schizoid and antisocial personality patterns and uncontrollable temper). Such a child may have a lighter complexion than unaffected siblings and often has blue eyes. He may also have microcephaly; eczematous skin lesions or dry, rough skin; and a musty (mousy) odor due to skin and urinary excretion of phenylacetic acid. Approximately 80% of these children have abnormal EEG patterns, and about one­third have seizures, usually beginning between ages 6 and 12 months.

Children with PKU show a precipitous decrease in IQ in their first year, are usually hyperactive and irritable, and exhibit purposeless, repetitive motions. They have increased muscle tone and an awkward gait.

Although blood phenylalanine levels are near normal at birth, they begin to rise within a few days. By the time they reach significant levels (approximately 30 mg/dl), cerebral damage has begun. Such irreversible damage probably is complete by age 2 or 3. However, early detection and treatment can minimize cerebral damage, and children under strict dietary control can lead normal lives.

Diagnosis

Most states require screening for PKU at birth; the Guthrie screening test on a capillary blood sample (bacterial inhibition assay) reliably detects PKU However, because phenylalanine levels may be normal at birth, the infant should be reevaluated after he has received dietary protein for 24 to 48 hours. The common practice of discharging new mothers from the hospital within 24 hours of delivery has resulted in failure to detect some infants with PKU For this reason, some states now require a minimum hospital stay of 48 hours after a vaginal delivery.

Adding a few drops of 10% ferric chloride solution to a wet diaper is another method of detecting PKU If the area turns a deep, bluish green, phenylpyruvic acid is present in the urine.

Detection of elevated blood levels of phenylalanine and the presence of phenylpyruvic acid in the infant's urine confirm the diagnosis. (Urine shouldalso be tested 4 to 6 weeks after birth because urinary levels of phenylpyruvic acid vary with the amount of protein ingested.)

Treatment

Harmful effects of PKU can be avoided by starting a special low-phenylalanine diet as soon as possible after birth. As phenylalanine is found in many proteins, protein-rich foods such as meat must be avoided and 'safe' proteins (usually specially formulated substitutes) taken instead. This diet should be followed long-term - the brain is only damaged while still growing and developing but there is some debate when it is safe to stop the diet.

It's important women with PKU follow the diet while pregnant, or they risk exposing their unborn child to high levels of the amino acid (this can lead to miscarriage, birth defects and brain damage in the child even if they haven't inherited PKU themselves).

Phenylketonuria Diet

The diet for the most severe form of phenylketonuria eliminates all of the very high protein foods since all protein contains phenylalanine. This means that all concentrated sources of protein must be eliminated from the diet in order to limit the amount of phenylalanine. Except in rare circumstances, the diet does not allow consumption of meat, fish, poultry, milk, eggs, cheese, ice cream, legumes, nuts, or many products containing regular flour. A synthetic formula is used as a nutritional substitute for the eliminated foods.

Prevention

Genetic counseling is recommended for prospective parents with a family history of PKU. The carrier state for PKU can be detected by enzyme assays, and PKU can be diagnosed prenatally.

It is imperative that a woman with PKU who becomes pregnant adheres closely to the special low-phenylalanine diet, since accumulation of phenylalanine will damage the unborn baby even if the baby has not inherited the abnormality.