Genetics and clinical enzymology

A large number of inherited disorders-the so-called inborn errors of metabolism-in which the characteristic metabolic and clinical abnormalities can be attributed to specific genetically determined deficiencies of particular enzymes, have now been identified: and new examples are currently appearing in the literature at a remarkable rate. Furthermore studies in vitro of the enzyme defect, as it occurs in erythrocytes, leucocytes, biopsy material from other tissues, or in fibroblasts grown in tissue culture, is already a critical diagnostic procedure for certain conditions. We may expect that this kind of in-vestigation is likely to become of increasing impor-tance in the future. A point of some interest which is beginning to emerge from such studies is the remarkable degree of genetic heterogeneity which may be uncovered when sensitive analytical procedures are applied to appropriate material from patients who have a deficiency of the same specific enzyme, but come from different families or different populations and are therefore not closely related genetically. For example, even in a condition as rare as methaemo-globinaemia due to a deficiency of methaemoglobin reductase several different sorts of enzyme defect, each apparently determined by a different abnor-mality of the gene, have now been identified in patients from different families (Kaplan and Beutler