Phenylketonuria: Epitome of Human Biochemical Genetics

IN the half century since Følling's original description, 1 phenylketonuria (PKU) has become a classic example of a genetic disorder because it illustrates three historic principles of human and medical genetics. 2 First of all, the disease is inherited as an autosomal-recessive trait according to Mendel's law of segregation, and it is listed (as entry 26160) in the modern catalogs of Mendelian Inheritance in Man . 3 Secondly, PKU is an "inborn error of metabolism," and it illustrates Garrod's cardinal principle of gene action: genetic factors specify chemical reactions and human biochemical individuality. 4 The extensive clinical and biochemical heterogeneity of the hyperphenylalaninemias of . . .