[Embryonic pathology caused by maternal phenylketonuria. A cause of underdiagnosed mental retardation. A report of 8 cases].

Objective: Maternal phenylketonuria (MPKU) is characterized by intrauterine growth retardation, microcephaly, congenital malformations (mainly cardiac defects), dysmorphic facial features and mental retardation. There are women of child-bearing age that do not know that they are affected by phenylketonuria (PKU) and their pregnancies could result in damage to the fetus expressed as different neurological and congenital abnormalities.
Patients and Methods: We report 8 patients from 4 families. The first family had two offspring with intrauterine growth retardation, microcephaly and psychomotor retardation. The second family consisted of a daughter with mental retardation (without further data), a second baby which died during the first day of life, and a third child which died at 7 months of age with cardiac defects, microcephaly and dysmorphic features. Another child had intrauterine growth retardation, microcephaly psychomotor retardation, dysmorphic features and cardiac defects (coarctation of the aorta and subaortic stenosis). The third family had a son with microcephaly and mental retardation. The fourth family had a boy that died at 3 weeks of age with microcephaly, dysmorphic facial features, congenital heart disease (mitral atresia and septal defects) and Meckel diverticulum and a girl 5 years of age with intrauterine growth retardation, microcephaly and mental retardation. In all cases the mothers were unaware that they were affected by PKU and had mild intellectual defects. Two of them had PKU phenotypes.
Conclusions: The offspring of PKU mothers untreated during pregnancy are affected by characteristic embriopathies related to the level of phenylalanine during pregnancy. In Spain, massive routine newborn screening was introduced around 1980-1985 and at present there are women of child-bearing age and are unaware that they are affected by the disease and that their pregnancies may result in fetal damage, as we demonstrate in these 8 patients. When faced with women with mental handicap or with antecedents of offspring with mental retardation, cardiac defects, microcephaly or intrauterine growth retardation, the determination of maternal phenylalanine concentrations is recommended. These teratogenic pathologies tend to disappear, but for the moment it is necessary to prevent this teratogenicity. The diagnosis is easy, avoids complementary exams, may help family studies and allows the implementation of dietary restriction during the subsequent pregnancy that would prevent fetal damage.