Problems in the chemical diagnosis of some hereditary metabolic diseases.

MODERN GENETICIST and his genetically oriented colleagues in 1Thi#{246}#{227}I medicine and biochemistry now believe that all inherited metabolic variations arise from alterations in the biochemical composition of the organism; it is assumed that these alterations are the direct result of variations in the gene or genes which determine the synthesis of a specific protein molecule. Some well-known hereditary metabolic disorders, such as phenylketonuria and alcaptonuria, have been shown to be inherited as simple recessives, with the fundamental enzyme defect attributable to the lack or alteration of a single gene at a single locus. There are other metabolic diseases, however, in which the mode of inheritance is probably more complex. Here, a particular biochemical phenotype may be either under the combined genetic influence of seevral distinct genes, or controlled by one gene at any of several loci. Because of the increasing clinical interest in the metabolic aspects of diseases, it is becoming more important for the clinical chemist to be aware of some of the problems associated with the diagnosis of hereditary diseases. This report will be primarily concerned with the significance and interpretation of variations in the urinary excre-