Phenylketonuria screening

NIH Consensus Statement Online Phenylketonuria screening and management. October 16-18 17 1-27, 2000. http //consensus.nih. gov/2000/2000phenylketonurial 13html.htm. Accessed 4/5/06. 

National Institutes of Health Consensus Development Conference Statement phenylketonuria screening and management, October 16-18, 2000. Pediatrics 2001 108(4) 972-82. 

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. 

A much more serious genetic disease, first described by Foiling in 1934, is phenylketonuria. Here the disturbance in phenylalanine metabolism is due to an autosomal recessive deficiency in liver phenylalanine hydroxylase (Jervis, 1954) which normally converts significant amounts of phenylalanine to tyrosine. Phenylalanine can therefore only be metabolized to phenylpyruvate and other derivatives, a route which is inadequate to dispose of all the phenylalanine in the diet. The amino acid and phenylpyruvate therefore accummulate. The condition is characterized by serious mental retardation, for reasons which are unknown. By the early 1950s it was found that if the condition is diagnosed at birth and amounts of phenylalanine in the diet immediately and permamently reduced, mental retardation can be minimized. The defect is shown only in liver and is not detectable in amniotic fluid cells nor in fibroblasts. A very sensitive bacterial assay has therefore been developed for routine screening of phenylalanine levels in body fluids in newborn babies. 

Infants with classic phenylketonuria (PKU) are normal at birth but if untreated show slow development, severe mental retardation, autistic symptoms, and loss of motor control. Children may have pale skin and white-blonde hair. The neurotoxic effects relate to high levels of phenylalanine and not to the phenylketones from which the name of the disease derives. Infants are routinely screened a few days after birth for blood phenylalanine level. Treatment consists of a life-long semisynthetic diet restricted in phenylalanine (smalt quantities are necessary because it is an essential amino acid). Aspartame (N-aspartyl-phenylalanine methyl ester), which is widely used as an artificial sweetener, must be strictly avoided by phenyiketonurics. 

The concentration of phenylalanine in the blood of neonates is used to screen for phenylketonuria (PKU). Explain the biochemical basis for the correlation of elevated blood phenylalanine concentration and PKU. Explain why restriction of dietary phenylalanine is critically important for youngsters with PKU. 

An inability to degrade amino acids causes many genetic diseases in humans. These diseases include phenylketonuria (PKU), which results from an inability to convert phenylalanine to tyrosine. The phenylalanine is instead transaminated to phenylpyruvic acid, which is excreted in the urine, although not fast enough to prevent harm. PKU was formerly a major cause of severe mental retardation. Now, however, public health laboratories screen the urine of every newborn child in the United States for the presence of phenylpyru-vate, and place children with the genetic disease on a synthetic low-phenylalanine diet to prevent neurological damage. 

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... 

W23. Woolf, L. I., Large-scale screening for metabolic disease in the newborn in Great Britain. In Phenylketonuria and Allied Metabolic Diseases (J. A. Anderson and K. F. Swaiman, eds.), pp. 50-61. US Dep. of Health, Educ., and Welfare, Childrens Bureau, US Govt. Printing Ofiice, Washington, D.C., 1967. 

Phenylketonuria [PKU (261600)1 is an autosomal recessive disease that causes severe mental retardation if it is undetected. Two normal parents are told by their state neonatal screening program that their third child has PKU. Assuming that the initial screening is accurate, what is the risk that their first child is a carrier for PKU ... 

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 ... 

As part of a standard neonatal screen, an infant is diagnosed with a loss of function genetic defect in the enzyme phenylalanine hydroxylase. Defects in this enzyme can result in a condition known as phenylketonuria (PKU), which results from the toxic effects of phenylalanine derived phenylketones. Fortunately, this condition can be managed by regulating the amount of phenylalanine provided in the diet. Which of the following nonessential amino acids will need to be supplied in the diet of this infant ... 

Sommer, S. S., et al., A novel method for detecting point mutations or polymorphisms and its application to population screening for carriers of phenylketonuria. Mayo Clin Proc, 1989. 64(11) p. 1361-72. 

If the genetic bases of phenotypes are known, disease risks may be assessed before disease onset. This is desirable only if preventive or therapeutic action can be taken. Otherwise, the psychological burden for the individual may be unwarranted. Ideally, preventive steps are undertaken in due time. Pre-symptomatic screening is applied, if disease prevails in famihes (for example, breast cancer and variation in estrogen receptor subunits or Hunting-ton s disease). The same is trae for prenatal and newborn screening, if family histories indicate the need (for example phenylketonuria, galactosemia, hypothyroidism). 

The detection of phenylketonuria was the first screening programme to be established. The screening test is based on the detection of increased phenylalanine concentration in the blood spot. 

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