Given our findings regarding genetic susceptibility to thrombosis in pseudotumor cerebri (PTC), we are studying the role of thrombosis in the development of PTC in nephropathic cystinosis. We are screening nephropathic cystinosis patients who develop PTC and control nephropathic cystinosis patients without PTC by using a thrombosis susceptibility panel including prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), activated protein C resistance (APCR), serum levels of protein C and S, antithrombin III, fibrinogen, total homocysteine, antiphospholipid antibodies (ACA panel and Lupus AC) and screening for FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, Prothrombin 20210 mutation and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in patients with severe homocysteinemia (>100 micro mol/l). To date, we have recruited five patients with Pseudotumor Cerebri with pre-existing Nephropathic Cystinosis. The thrombosis screening panel revealed shortened thrombin time (TT) in two patients, high titer Anticardiolipin (ACA) IgM antibodies in one patient and. Activated Protein C Resistance (APCR) in one patient. Thrombin time measures the rate of fibrin monomer polymerization and is the most sensitive screening test for decreases or abnormalities in fibrinogen. The shortened TT demonstrates an acceleration of fibrin monomer polymerization leading to thrombotic tendency. Activated protein C resistance is a condition which leads to a hypercoagulable state with an increased risk for venous thrombosis and IgM isotype of ACA has been shown to be associated with venous thrombosis. Method Evolved for Recognition of Thrombophilia (MERT) Dogulu, Chan, Rennert, in collaboration with Su Venous thrombosis affects 1 per 1000 individuals annually and is one of the leading causes of mortality and morbidity resulting in approximately 300,000 hospitalizations and 50,000 fatalities per year in the United States alone. It is, however, an avoidable disease if currently available prophylactic treatment is instituted. We have devised an approach (patent pending) that will allow prediction and accurate assessment of hereditary thrombophilia in several ethnic populations by rapid, concurrent screening of an array of all known 143 venous thrombosis associated recurrent mutations and polymorphisms in 8 different genes in order to develop stratification protocols for risk-adapted prophylaxis.
