Child health and life expectancy improved together in many societies in the 20th century. As the incidence of diseases with major extrinsic causes declined, the heritability of disease as a whole increased. Accordingly, the genetic (intrinsic) causes of disease have become important. The genome project is an international venture out of which will come new knowledge about the biological basis of health and disease, and technologies to apply that knowledge in medicine and other disciplines. Phenylketonuria (PKU) at one time was seen only as a rare inborn error of metabolism causing severe mental retardation. Yet, the gene frequency is about 1% in Caucasian and Oriental populations, higher still in some populations with particular histories that have enhanced gene frequency. These genetic facts make PKU a paradigm in human genetics. This genetic disease, for which it was thought there was nothing to be done, has yielded to inquiries at clinical, metabolic, protein (enzyme) and DNA (PAH gene) levels. Results have shown that, early diagnosis (by population screening) and treatment (by low phenylalanine diet) largely prevents mental retardation. DNA analysis reveals particular associations between PKU mutations, RFLP haplotypes and populations; these associations are relevant for counseling. PKU illustrates well how medical science, molecular biology and gene mapping can improve knowledge and contribute to child health.