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Hereditary absence of adenosine deaminase activity in erythrocytes was found in an infant with severe combined immunodeficiency. Immunoglobulins were markedly decreased. Lymphocytes failed to transform with either phytohemagglutinin or concanavalin. At autopsy the thymus was rudimentary and there was a striking absence of lymphoid elements throughout the lymphoreticular system. The costochondral junction of the ribs showed widening and cupping of the metaphyseal plates, and the metaphysis of the long bones demonstrated lucent bands suggestive of a defect in ossification. The association of combined immunodeficiency with the genetically determined absence of erythrocyte-type adenosine deaminase appears now to be a specific clinical entity.

Eight enzymes: phosphoglycerate kinase, soluble glutamic oxaloacetic transaminase, glutamic-pyruvic transaminase, isocitric dehydrogenase, adenosine deaminase, peptidase A, peptidase B, and “indophenol oxidase” were examined electrophoretically in red cells from 160 Taiwanese samples. Only GPT and ADA were found to exhibit polymorphism, the gene frequency for GPT1 and ADA1 being about 0.51 and 0.95 respectively. No S-GOT variation was identified in this particular population, although an atypical gene frequency of 0.02 was anticipated from prior surveys of Asiatic groups. These samples were collected in 1960 and preserved in glycerol indicating that meaningful results can be obtained on specimens stored for prolonged periods.

THE Lyon hypothesis of X chromosome inactivation predicts that in mammalian females, somatic cells are mosaic with respect to whether the active X chromosome is of maternal or paternal origin and that this chromosomal mosaicism is heritable somatically1. Studies of cell clones derived from females who were heterozygous for genes at one of several X-linked loci2–6 have provided good evidence for such mosaicism. Proof that only one of the two X chromosomes, however, is active in any given cell rests on the demonstration that the cell or its clone expresses all of the X-linked genes from one parent and none from the other parent. For this purpose it is useful to examine cloned cells from female subjects for genetic markers representing allelic genes at two or more of the parental loci. This study was undertaken to determine whether genes at the X-linked loci for glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase (PGK) are consistently expressed in the eis position in cloned cells as would be expected from a single parental contribution.

Adenosine deaminase (ADA) deficiency is now recognized as a cause of one type of severe combined immunodeficiency (CID). Of major interest is the genetic transmission and the identification of heterozygotes for ADA deficiency. A large family in which an infant had died with CID aud ADA deficiency was studied by determining the enzyme activity and isoenzyme pattern of ADA in red cells. By electrophoresis three red cell phenotypes, ADA 1, ADA 2 and ADA 2-1 could be recognized in the family. In one mating a father had ADA 2-1, the mother had ADA 1, and one of their three children had ADA 2. The mother and child had ADA activity below the normal range. This anomalous inheritance could only be explained by the existence of a “silent” allele (ADA°) at the structural locus for red cell ADA. Each parent of the affected child had ADA values 2.3 and 3.8 SD below the mean of 67 normal persons (36.1 U/gm Hb; 22.5-58.1 (± 2SD)). Nine additional family members in 3 generations could be recognized as having ADA values similar to the parents' values. The mean activity of the combined heterozygotes was (19.2 U/gm Hb; 14.0-24.4 (± 2SD)). One sibling of the proband could not be accurately classified as normal or heterozygous. Our data suggests that ADA deficiency is autosoinally transmitted and heterozygotes for ADA° can be correctly detected with a probability of 90 percent.