Pku and Lipids

LITERATURE REVIEW

Phenylketonuria

Phenylketonuria (PKU) is an inborn error of phenylalanine (PA) metabolism that occurs once in approximately seven thousand to one in fifteen thousand live births (Bickel et al, 1981; Elsas and Acosta, 1994). PKU is inherited as an autosomal recessive disorder and occurs in all ethnic groups (Eisensmith and Woo, 1992; Eisensmith et al, 1992). One in fifty people is a heterozygous carrier of this disease (Pietz, 1998). PKU is caused by a deficiency or absence of hepatic phenylalanine hydroxylase (PAH; Enzyme commission 1.14.16.1), which converts PA, an essential amino acid in humans, to tyrosine (Jervis, 1953; Hsia, 1966; Guttler et al, 1987). The deficiency or absence of PAH causes a metabolic block in PA catabolism which results in accumulation of PA and reduced levels of tyrosine plasma and urine (Jervis, 1940).

In untreated PKU, plasma concentrations of PA are sufficiently high such that alternate pathways of PA metabolism are activated leading to formation of PA metabolites, such as, phenylpyruvate, phenylacetate, phenylacetylglutamine, and phenyllactate (Bowden and McArthur, 1972). High levels of these metabolites if not immediately diagnosed and treated in infancy can cause severe central nervous system abnormalities (Burgard et al, 1996; Okano et al, 1991). Although no abnormalities are present at birth, if untreated, the clinical phenotype of PKU infants may be hypopigmentation; peculiarities in gait, stance, and sitting posture; eczema; microencephaly; seizures; and mental retardation with an intelligence quotient below fifty (Guldberg et al, 1998; Holtzmann et al, 1986, Waisbren and Levy, 1991; Villasana et al, 1989). Fortunately, all infants born in North America are screened for this disease by routine analysis of blood for PA concentrations. As a result of screening newborns for PKU, the severity of symptoms associated with this disease has been reduced.

The treatment of PKU individuals involves the reduction...