MedGen

Heterozygous protein C deficiency is characterized by recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic (Millar et al., 2000). Individuals with decreased amounts of protein C are classically referred to as having type I deficiency and those with normal amounts of a functionally defective protein as having type II deficiency (Bertina et al., 1984). Acquired protein C deficiency is a clinically similar disorder caused by development of an antibody against protein C. Clouse and Comp (1986) reviewed the structural and functional properties of protein C and discussed both hereditary and acquired deficiency of protein C. [from OMIM]

Heterozygous protein S deficiency, like protein C deficiency (176860), is characterized by recurrent venous thrombosis. Bertina (1990) classified protein S deficiency into 3 clinical subtypes based on laboratory findings. Type I refers to deficiency of both free and total protein S as well as decreased protein S activity; type II shows normal plasma values, but decreased protein S activity; and type III shows decreased free protein S levels and activity, but normal total protein S levels. Approximately 40% of protein S circulates as a free active form, whereas the remaining 60% circulates as an inactive form bound to C4BPA (120830). Zoller et al. (1995) observed coexistence of type I and type III PROS1-deficient phenotypes within a single family and determined that the subtypes are allelic. Under normal conditions, the concentration of protein S exceeds that of C4BPA by approximately 30 to 40%. Thus, free protein S is the molar surplus of protein S over C4BPA. Mild protein S deficiency will thus present with selective deficiency of free protein S, whereas more pronounced protein S deficiency will also decrease the complexed protein S and consequently the total protein S level. These findings explained why assays for free protein S have a higher predictive value for protein S deficiency. See also autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514), which is a more severe disorder. [from OMIM]