A survey of some hereditary metabolic diseases.

It has been recognized for many years that there are a few entities in which a characteristic combination of clinical and chemical abnormalities is genetically transmitted. The number of diseases and apparently harmless metabolic anomalies which have been recognized as belonging to this group has increased considerably since Garrod in 190225 described alkaptonuria as an ' inborn metabolic error'; and there are others such as diabetes mellitus, the causation of which appears to be at least partly hereditary. The original hypothesis of a genetically determined enzyme block has proved a fruitful one, ana it has received experimental support from the study of the specific blocks in metabolism which occur in mutant strains of micro-organisms such as Neurospora. Some inherited chemically characteristic diseases are due to a failure of specific renal tubular reabsorptive processes and presumably result ultimately from an abnormality of the enzymic mechanisms which effect active transport across these cells. All enzymes are probably proteins and the inborn enzyme defects are therefore specialized examples within the group of diseases which are due to inherited abnormalities of protein synthesis. Limitation of space prevents a discussion of other inherited protein abnormalities such as the haemoglobinopathies, the congenital plasma protein deficiencies and the deficiencies of the bloodclotting factors. The renal tubular reabsorption defects (e.g. cystinuria) have also been omitted for this reason.