The Problem of Maternal Phenylketonuria

Maternal Phenylketonuria Collaborative Study (MPKUCS)—The 'outliers'

“…The Maternal Phenylketonuria (PKU; McKusick 261600) Collaborative Study (1984^2002) involved 414 offspring from 515 pregnancies and 100 controls. The offspring outcome data (Koch et al 2003) generally support the literature (Drogari et al 1987;Frankenburg et al 1968;Howell and Stevenson 1971;Hsia 1970;Lenke and Levy 1980;Levy and Ghavami 1996;Levy et al 1992;Lipson et al 1984;Perry et al 1973;Pitt and Gooch 1974;Rouse et al 1997), which indicates that virtually all offspring of untreated, late-treated or poorly treated women with 'classical phenylketonuria' (Table 1) have mental retardation (MR) and many have microcephaly, intrauterine growth retardation (IUGR), congenital heart disease (CHD) and speci¢c facial dysmorphism. It has been pointed out, however, that milder forms of MPKUö'mild/atypical PKU' and 'non-PKU mild hyperphenylalaninaemia' (MHP) ( Table 1)öhave better offspring outcome even if untreated or poorly treated during pregnancy (Koch and Blaskovics 1982;Levy and Waisbren 1984;Levy et al 1994a,b;Perry et al 1973;Woolf et al 1961).…”

“…By far the great majority of o¡spring from untreated maternal classical PKU are profoundly damaged (Angeli et al 1974;Drogari et al 1987;Frankenburg et al 1968;Howell and Stevenson 1971;Hsia 1970;Lenke and Levy 1980;Lipson et al 1984;Pitt and Gooch 1974). The ¢rst well-documented report of a normal o¡spring from a mother with untreated classical PKU was by Partington (1962).…”

Genetic effects of maternal inbreeding in man on congenital abnormality, mental defect, infertility, and prenatal death

“…Some genotypes of the mothers may cause anatomical, physiological or biochemical changes in their bodies, which in turn produce adverse effects on the fetal environment or increase susceptibility of fetuses to harmful agents inducing fetal, perinatal or neonatal deaths, or congenital abnormalities in genotypically normal fetuses. Births of malformed and mentally deficient children from phenylketonuric mothers is one of the most remarkable examples (Fisch and Anderson, 1971;Pitt and Gooch, 1974). In these occassions mothers having such genotypes may manifest some abnormal signs or may appear almost normal.…”

Results of screening for phenylalanine and other amino acid disturbances among pregnant women

“…In many cases the toxic effect causes a spontaneous abortion, while in other cases an increased incidence of intrauterine and postnatal growth retardation, as well as of congenital anomalies, skeletal, cardiac, brain and other malformations, were observed. In most cases mental retardation and microcephaly were found (Huntly and Stevenson, 1969;Hansen, 1970;Hsia, 1970;Pitt and Gooch, 1972;MacReady and Levy, 1972;Yu and O'Halloren, 1970;Cockburn et al, t972).…”