Eva Gross Friedman

Preliminary report on the effects of diet discontinuation in PKU

A collaborative study of diet discontinuation in children with PKU was initiated in 1973. Children treated with the phenylalanine-restricted diet since early infancy were randomly assigned to continue or discontinue dietary therapy at age 6 years after parental consent was obtained. The 115 children participating in this study range in age from 8 to 13 years. At 6 years of age, the IQ of continuers and discontinuers was 101 and 97, respectively. At 8 years, WISC Full-Scale IQ scores adjusted for mean differences on the 6-year Stanford-Binet IQ were 101 for continuers and 98 for discontinuers (P = 0.075). School performance measured by the Wide Range Achievement Test showed significant differences on reading (3.9 vs 3.2) and spelling (3.3 vs 2.9) grade placement, although scores were above actual grade placement (2.7 vs 2.6) for both groups. Continuers and discontinuers were not different in arithmetic scores, with performance at grade placement of 2.7 and 2.6 respectively. Although these data are preliminary in nature, they suggest that subtle changes in cerebral function may occur in children with PKU in whom the phenylalanine diet has been discontinued.

The International Collaborative Study of Maternal Phenylketonuria: status report 1998.

Abstract The Maternal Phenylketonuria Study began in 1984 and during the intervening years, 572 pregnancies in hyperphenylalaninemic women and 99 controls and their outcomes have been evaluated. Among hyperphenylalaninemic women who delivered a live infant, only 15.9% were treated and in metabolic control preconceptually, however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptually treated pregnancies with well controlled phenylalanine restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring, however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. Conclusion The recommended level of blood phenylalanine during pregnancy is 120–360 μmol/l. Best results were obtained by close cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria.

The International Collaborative Study of Maternal Phenylketonuria status report 1998

The Maternal PKU Study began in 1984 and during the intervening years, 572 pregnancies in women with hyperphenylalaninemia (HPA) and 99 controls and their outcomes have been evaluated. Among Women with HPA who delivered a live infant, only 15.9% were treated and in metabolic control preconceptionally; however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptionally treated pregnancies with well-controlled phenylalanine-restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring; however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. The recommended level of blood phenylalanine during pregnancy is 120–360 μmol/L. Best results were obtained by close cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria. MRDD Research Reviews 1999;5:117–121.

Preliminary report of the effects of diet discontinuation in phenylketonuria

The accepted therapy for phenylketonuria (PKU) (McKusick 26160) is the use of a diet restricted in phenylalanine (phe). In the United States, dietary therapy has usually been terminated between four and six years of age; however, some clinicians prefer to delay diet discontinuation until adolescence or later. Murphy (1969) initially suggested that termination of dietary therapy during childhood might be harmful. Dietary termination in two children was followed by adverse changes in behaviour and reduced intellectual performance. Subsequently, Cabalska et al. (1977) and Smith et al. (1978) recorded similar findings. The Collaborative Study of Children Treated for Phenylketonuria (Williamson et al., 1977; Koch et al., 1973) has begun to evaluate the effects of discontinuing dietary therapy at age six years (Williamson et al., 1979). This report presents findings on academic ability of children off diet from age six to eight years in comparison to a group maintained on treatment.

Treatment Outcome of Maternal Phenylketonuria

Our experience to date with 40 pregnancies in 13 women with hyperphenylalaninemia indicates that to prevent mental retardation in their children, maternal phenylalanine levels of 120–600 umol/L are needed, in addition to a newborn screening program. While treatment results to date are preliminary, it appears that the phenylalanine‐restricted diet is of value and should be instituted as soon as pregnancy is planned by phenylketonuric women. There is much to be learned by study of these women and referral to a collaborating center in the National Maternal PKU Collaborative Study is recommended.