Maternal Phenylketonuria and Hyperphenylalaninemia

Abstract

Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.

Maternal effects on mouse brain weight

“…Although the influence of the BALB/c maternal environment may in turn reflect autosomal genetic factors possessed by the mother, as has been shown for certain Mendelian gene mutations 10,16 , the maternal environment effect on offspring development is not the same kind of genetic influence on the growing mouse as is the mouse's own set of genes inherited via egg and sperm. From the perspective of the growing mouse it is strictly an environmental influence, although some human theorists might prefer to see it as an indirect genetic influence.…”

Genetic Epidemiology

“…It has been shown that persistent maternal hyperphenylalaninemia during pregnancy is harmful to the fetus, leading to increased risk of cardiac anomalies, intrauterine growth retardation, microcephaly, and mental retarda tion. Dietary therapy instituted after pregnancy was detected was not effective in preventing these cogenital defects (114). It has been suggested that restrict ing the diet both prior to and during pregnancy may be effective.…”

Prevention: Rhetoric and Reality

“…In principle, it should prove possible to reduce risk by putting women with this disorder on a phenylalanine low diet before they attempt to become pregnant. If the diet is introduced after pregnancy occurs, it brings little benefit because of damage done during the first six weeks of fetal development (Lenke & Levy 1980). Preventing environmental hazards to the brain Accidents and poisonings are the leading causes of childhood and adolescent mortality and morbidity in the United States.…”