title: Diet, genetics, and mental retardation interaction between phenylketonuric heterozygous mother and fetus to produce nonspecific diminution of IQ: evidence in support of the justification hypothesis.
abstract: The justification hypothesis postulates that an individual genetically deficient in the synthesis of any of the 12 nonessential amino acids requires that amino acid in the diet just as a normal individual requires any essential amino acid. The deficiency of that single amino acid causes diminished protein synthesis. The hypothesis proposes that mental retardation develops during the late stage of fetal development, when the brain is growing most rapidly, as a result of the inability of the mother to deliver an appropriate amount of that nonessential amino acid to her fetus who, in turn, is unable to correct for this deficiency due to his genetic constitution. A paradigm is provided by the disease phenylketonuria in which the homozygote lacks the enzyme for synthesis of the nonessential amino acid tyrosine. By measuring the appearance of tyrosine in the plasma after an oral dose of phenylalanine, it is possible to show differential capability among siblings of known phenylketonuric children, in the expected Mendelian ratio. The mean IQ of the two-thirds of the siblings who were least able to convert phenylalanine to tyrosine (presumably heterozygotes) was 10 points lower than the mean IQ of the "normals," who were most able to synthesize tyrosine. The difference is statistically significant (P <0.01). The mean maternal IQ was halfway between that of the heterozygote group and that of the normal group, confirming the prediction of maternal-fetal interaction.
mesh_terms: D004032:Diet; D005260:Female; D006579:Heterozygote; D006801:Humans; D007360:Intelligence; D008431:Maternal-Fetal Exchange; D010649:Phenylalanine / Q000378:metabolism*; D010661:Phenylketonurias / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D014443:Tyrosine / Q000378:metabolism*; D014888:Wechsler Scales
chemical_list: D014443:Tyrosine; D010649:Phenylalanine