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.
PKU is transmitted by an autosomal recessive gene on chromosome 12. Patients with this disorder have insufficient hepatic phenylalanine hydroxylase, an enzyme that acts as a catalyst in the conversion of phenylalanine to tyrosine. As a result, phenylalanine and its metabolites accumulate in the blood, eventually causing mental retardation if left untreated. The exact biochemical mechanism that causes this retardation is unclear.
In the United States, this disorder occurs in 1 in approximately 14,000 births. (About 1 person in 60 is an asymptomatic carrier.) The gene is most common in Ireland, Scotland, Belgium, and West Germany and rare in Blacks, Asians, Native Americans, Finns, and Ashkenazi Jews.
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 typically 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 one-third 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.
All 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 neonate 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 neonates 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.
Chorionic villi sampling can be used to detect fetal PKU as a prenatal diagnosis. Enzyme assay can be used to detect the carrier state in parents.
Treatment consists of restricting dietary intake of the amino acid phenylalanine to keep phenylalanine blood levels between 3 and 9 mg/dl. Because most natural proteins contain 5% phenylalanine, they must be limited in the child's diet. An enzymatic hydrolysate of casein, such as Lofenalac powder or Pregestimil powder, is substituted for milk in the diets of affected infants. This milk substitute contains a minimal amount of phenylalanine, normal amounts of other amino acids, and added amounts of carbohydrate and fat. Dietary restrictions usually continue throughout life.
The special diet for PKU calls for careful monitoring. Because the body doesn't make phenylalanine, overzealous dietary restriction can induce phenylalanine deficiency, producing lethargy, anorexia, anemia, rashes, and diarrhea.
In caring for a child with PKU, it's especially important to teach both the parents and child about this disease and to provide emotional support and counseling. (Psychological and emotional problems may result from the difficult dietary restrictions.)
❑ Emphasize to the child and his parents the critical importance of adhering to the special diet. The child must avoid breads, cheese, eggs, flour, meat, poultry, fish, nuts, milk, legumes, and phenylalanine sugar substitutes.
❑ Inform the parents that the child will need frequent tests for urine phenylpyruvic acid and blood phenylalanine levels to evaluate the diet's effectiveness.
❑ As the child grows older and is supervised less closely, his parents will have less control over what he eats. As a result, deviation from the restricted diet becomes more likely, as does the risk of brain damage. Encourage the parents to allow the child some choices in the kinds of low-protein foods he wants to eat; this will help make him feel trusted and more responsible.
❑ Teach the parents about normal physical and mental growth and development so that they can recognize any developmental delay that may point to excessive phenylalanine intake.
❑ Refer females with PKU who reach reproductive age for genetic counseling because recent research indicates that their offspring may have a higher-than-normal incidence of brain damage, mental retardation, microcephaly, and major congenital malformations, especially of the heart and central nervous system. Such damage may be minimized with a low-phenylalanine diet before conception and during pregnancy, but even patients under good control remain at increased risk for offspring with this defect.
Review other book chapters online related to Phenylketonuria:
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: Professional Guide to Diseases (Eighth Edition) Authors: Springhouse Publisher: Lippincott Williams & Wilkins Copyright: 2005 ISBN: 1-58255-370-X 
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