Inborn errors of lysosomal catabolism - principles of heterozygote detection

Carriers of an inborn error of lysosomal catabolism can be recognized, as they have enzyme levels approximately half those of normal individuals. Of the various tissues readily available for assay, plasma and leukocytes and, in some situations, tears are preferred. Although mixed leukocytes have proved satisfactory in Tay-Sachs screening programs, purified preparations of granulocytes or lymphocytes will allow better discrimination in most situations. Enzymes are assayed relative to some other reference parameter which must be a constant or highly correlated with test enzyme activity. In the 2 mass screening programs in operation, β-hexosaminidase A and α-mannosidase have both been assayed relative to total β-hexosaminidase activity. Carrier detection is particularly important in X-linked diseases. The techniques used mostly involve hair roots or fibroblasts and depend on random inactivation of the X chromosome. In the mucolipidosis II and III, in which there are a number of deficient enzymes in cells carriers may be identified on the basis of the ratio of β-hexosaminidase I₁ and I₂ to total hexosaminidase.