Genetics of thrombosis in pseudotumor cerebri of nephropathic cystinosis

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Using a thrombosis susceptibility panel, we screen nephropathic cystinosis patients who develop PTC as well as control nephropathic cystinosis patients without PTC. The panel includes 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). In patients with severe homocysteinemia (greater than or equal to 100 micro mol/l), we screen for the FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, prothrombin 20210 mutation, and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms. To date, we have recruited five patients with PTC 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 (a shortened TT demonstrates an acceleration of fibrin monomer polymerization, which contributes to thrombotic tendency). Activated protein C resistance is a condition that leads to a hypercoagulable state with an increased risk for venous thrombosis; the IgM isotype of ACA has been shown to be associated with venous thrombosis. Thus, there appears to be no single risk factor for the development of PTC in the patients studied.