Phenylketonuria testing

A newborn boy appeared to be healthy and was discharged from the hospital. He was breast-fed by his mother. A blood sample collected for galactosemia and phenylketonuria testing per state law indicated lowered levels of galactose-1-phosphate uridyltransferase in the child s red blood cells. Discuss the following ... 

Luteinizing hormone assay Mammography Obstetric ultrasonography Papanicolaou smear Phenylketonuria test Pregnancy tests Pregnanediol Progesterone assay Prolactin... 

Phenylpyruvic acid can cause mental retardation m infants who are deficient m the enzymes necessary to convert l phenylalanine to l tyrosine This disorder is called phenylketonuria, or PKU disease PKU disease can be detected by a simple test rou tmely administered to newborns It cannot be cured but is controlled by restricting the dietary intake of l phenylalanine In practice this means avoiding foods such as meat that are rich m l phenylalanine... 

Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders. 

Phenylalanine hydroxylase (PH) which requires tetrahydrobiopterin (BH4) as a cofactor, is defective in cases of phenylketonuria (PKU). This is a rare (prevalence 1 / 15 000 in the United Kingdom) genetic condition characterized by fair complexion, learning difficulties and mental impairment. If PH is either not present in the hepatocytes or is unable to bind BH4 and is therefore non functional, phenylalanine accumulates within the cells. Enzymes in minor pathways which are normally not very active metabolize phenylalanine ultimately to phenylpyruvate (i.e. a phenylketone). To use the traffic flow analogy introduced in Chapter 1, the main road is blocked so vehicles are forced along side roads. Phenylpyruvate is excreted in the urine (phenyl-ketone-uria), where it may be detected but a confirmatory blood test is required for a reliable diagnosis of PKU to be made. 

Drug/Lab test interactions Phenothiazines may produce false-positive phenylketonuria (PKU) test results. Phenothiazines may cause false-positive pregnancy test results. 

During the past 20 years, neonatal screening programs using the Guthrie test for inborn errors of metabolism such as phenylketonuria have become more widely used. The characteristics of diseases in which mass screening is... 

Fiege B, Bonafe L, Ballhausen D, et al. Extended tetrahydrobiopterin loading test in the diagnosis of cofactor-responsive phenylketonuria A pilot study. Mol Genet Metab 86 s91-s95,... 

C-7) Phenylketonuria (deficiency of phenylalanine hydroxylase). Occasionally, the defect is not in the enzyme but in the ability to regenerate tetrahydrobiop-terin, which is also necessary for the reaction. There is a buildup and excretion of phenylpyruvate in the urine, giving it a mousy odor. Mental retardation is a prominent feature. Diagnosis can be made by routine urine testing for phenylpyruvate or serum testing for elevated phenylalanine levels. The condition is treated with a diet low in phenylalanine. Sometimes, tetrahydrobiopterin deficiency may be treated by supplying biopterin,... 

The incidence of phenylketonuria is about 1 in 20,000 newborns. The disease is inherited in an autosomal recessive manner. Heterozygotes, who make up about 1.5% of a typical population, appear normal. Carriers of the phenylketonuria gene have a reduced level of phenylalanine hydroxylase, as indicated by an increased level of phenylalanine in the blood. However, this criterion is not absolute, because the blood levels of phenylalanine in carriers and normal people overlap to some extent. The measurement of the kinetics of the disappearance of intravenously administered phenylalanine is a more definitive test for the carrier state. It should be noted that a high blood level of phenylalanine in a pregnant woman can result in abnormal development of the fetus. This is a striking example of maternal-fetal relationships at the molecular level. Table 23.3 lists some other diseases of amino acid metabolism. 

The screening test for phenylketonuria (PKU) is called the Guthrie test. Based on this screening method, which of the following is the most likely explanation of a false-negative screen in a newborn ... 

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