Phenylketonuria (PKU)

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Phenylketonuria (PKU) is an inborn error of metabolism transmitted genetically. Boy with untreated PKU. He usually shows electroencephalogram abnormalities, and may show a reduction in head size.  He is likely to have a distinct, musty, unpleasant odor, and to have lighter hair and less skin pigment than other members of his familyBoth parents must be carriers of the gene to produce a child with this condition. When both parents are carriers of the gene, chances of an affected child occurring are one in four for each pregnancy. There is a 50% chance that a child born to these parents will be a carrier of the phenylketonuria gene.

There are no known clinical signs of PKU present in a newborn. There is nothing in the appearance or behavior of a newborn phenylketonuric which distinguishes a newborn with PKU from a normal newborn. However, early in the first year of life, the phenylketonuric may develop symptoms such as marked irritability, severe vomiting, exzema, seizures and a musty odor. Serum phenylalanine tests are required to validate any of these suspicious symptoms.

Unfortunately, warning symptoms may not be prominent early in life, and deviations from normal may not be observed until the child is well along in their first year. Delayed ability to sit alone may be the first sign that something is wrong with a child. The untreated phenylketonuric may not walk until early childhood; some may never learn to walk. Motor development is slow but of secondary concern in the presence of the profound intellectual disability which is displayed. The child is irritable and often displays agitated behavior. The child usually shows electroencephalogram abnormalities, and may show a reduction in head size. The child is likely to have a distinct, musty, unpleasant odor, and to have lighter hair and less skin pigment than other members of their family.

The essential amino acid, phenylalanine, is contained in the protein fraction of all foods in the human diet. The phenylketonuric is born with a defect in their ability to produce the liver enzymes necessary for the metabolism of phenylalanine. Subsequent mental deterioration is a consequence of the accumulation of phenylalanine in the blood and tissues of the body and therefore related to an inherited liver dysfunction.

The phenylketonuric child's gastrointestinal processes are normal. Protein molecules are broken into their component amino acids in the intestinal tract and transported to the liver. It is at this point that the phenylketonuric child deviates from normal. The liver of a phenylketonuric child is able to produce only a small quantity of the enzyme necessary to convert phenylalanine to tyrosine and its metabolites (such as pigment and hormones). In the absence of the enzyme, phenylalanine and its metabolites accumulate in the blood and body tissues. Large amounts of by-products are excreted through the urine, but not enough to keep the serum level below the toxic point for the newborn's developing brain and nervous system.

The initial objective of treatment is to reduce the concentration of phenylalanine in the blood by reducing phenylalanine intake. After a diagnosis of PKU, the child's regular feeding will be a low phenylalanine formula carefully supplemented with other food sources of protein. This special formula, which contains significantly less phenylalanine that other formulas or milks is the main source of protein for a phenylketonuric infant. Blood tests must be performed often to determine how rapidly the serum phenylalanine level is decreasing. Care must be taken to prevent this level from falling below the therapeutic range.

After the initial reduction in serum phenylalanine levels, the objective is to adjust the phenylalanine intake to maintain the serum level within a range that will assure sufficient phenylalanine for growth, without permitting toxic accumulation of phenylalanine or its abnormal metabolites. Close supervision of diet and medical follow-up is necessary to maintain this delicate balance. 

Screening for PKU in Texas was begun in 1965. Diagnosed cases are detected through the Newborn Screening Program, Texas Department of State Health Services (DSHS), in cooperation with the Newborn Screening Laboratory, DSHS.

The screening test for PKU initially used by DSHS was developed by Doctor Robert Guthrie and was done on a filter paper blood spot. Known as the Guthrie Test, it was an inhibition assay test which utilized the bacterial metabolism of Bacellus subtiles.

Presently, the PKU test is done as a part of the Tandem Mass Spectometry (MS/MS) Panel. MS/MS is an analytical technique that measures the mass-to-charge ratio of charged particles. This is a technique that can measure the concentration of metabolites phenylanaline and other amino acids at the same time. Test results of phenylalanine greater than 4 mg/dl is considered out of range and reported to the health care provider. If a test result is reported as greater than 4 mg/dl, the health care provider is asked to submit a confirmatory 1-2 cc serum specimen to a clinical laboratory for more specific analysis of phenylalanine levels.

When out of range results are first discovered and reported, additional services are coordinated by telephone. Information concerning the name of a metabolic specialist at a diagnostic center in the geographic location closest to the patient is offered to the health care provider. The metabolic specialist is also notified of out of range test results.  The NBS Program will continue to track the baby until the baby is connected to an appropriate metabolic specialist. The baby will be followed by the NBS Program during their childhood by contact with their metabolic specialist. The Newborn Screening Laboratory, DSHS, will monitor serum specimens for phenylalanine levels to assist in diagnosing a new case or monitoring a child who has already been diagnosed, if requested.

Phenylketonuria should not be diagnosed or a child started on special formula on the basis of testing done at DSHS alone; there are many reasons a NBS may be out of range for phenylalanine; treatment will depend on childs ultimate diagnosis. Further testing of blood and urine should be done at a diagnostic center where more specific laboratory testing, examination by a metabolic specialist, evaluation by a nutritionist, and genetic counseling are available.

It is essential that follow-up be prompt on abnormal phenylalanine screens. Recent studies have shown that each day treatment is delayed on a child with classic PKU, furthers the chance of irreversible mental damage.

DSHS offers additional services to the primary care providers to assist in follow-up care of phenylketonuric children. The NBS and Genetics Unit maintains a list of genetic services throughout Texas and offers this information to the physician as indicated. The Newborn Screening Program provides literature, videos, and speakers for seminars to health care providers concerning newborn screening. The Newborn Screening Program provides assistance with PKU formula costs and confirmatory testing for families who qualify for the Newborn Screening Benefits Program. Individuals who qualify have an income level up to 350% of the federal poverty level, no other medical coverage for these services, and not be eligible for Medicaid, WIC, CSHCN, or CHIP.  

Last updated December 21, 2010