Genetics and the lipidoses

Formal genetic analyses of family data in cases of errors of lipid metabolism are able to distin‐guish monogenic vs. multigenic and nongenetic disorders. These data, together with population data, provide criteria for the homogeneity of cases which can be useful in the interpretation of biochemical findings. The peculiarly elevated incidence of three main genotypes of sphingo‐lipidoses among Ashkenasic Jews has no reason‐able explanation except for heterozygote selection. This inference has strong implications for the biochemist in that it suggests a) the existence of some biochemical abnormality is common among the heterozygotes for these conditions and b) the utility of such a heterozygote abnormality in the defense of the body against some adverse en‐vironmental stress, such as some specific infectious disease. The detection of heterozygous carriers by bio‐chemical means could be important not only for this reason but also as a means for anticipating marriages which may produce a lethal lipidosis. Finally, as long as preventive measures are either imperfect or not practiced, major attention is directed toward therapy, which in turn requires not only more knowledge of the basic defect but awareness of the fact that such knowledge may not be helpful without the development of more advanced devices than those employed in, for ex‐ample, phenylketonuria or galactosemia. The deep‐seated nature of the presumed lesions in the lipidoses seems to require a different type of corrective measure, such as gene replacement or transformation.