Thrombomodulin and ristocetincofactor in homocystinuria: a study in two siblings.

Homocystinuria due to cystathionine-beta-synthase deficiency (CBS-def-HOCY) initially often presents with vascular disorders, e.g. thromboembolic events. The measurement of vascular endothelial markers in plasma could help to assess endothelial damage. We determined von Willebrand factor (measured as Ristocetincofactor, RiCoF) and thrombomodulin (TM), two endothelial cell markers to our knowledge not measured systematically before in homocystinuria patients in a longitudinal study of two homocystinuric patients: Patient1 with thromboembolic disease and his asymptomatic sister, patient2. Before start of therapy in patient 1, TM and RiCoF levels both were increased. In patient 2 a moderately elevated RiCoF and a normal level of TM were found. Vitamin therapy with 15 mg folate and 600 mg pyridoxine per day led to almost complete normalization of amino acids in urine and plasma, and complete normalization of RiCoF and TM levels in both patients. Thus, TM and RiCoF elevations demonstrate that CBS-def-HOCY leads to endothelial cell damage, which resolved under vitamin therapy in the patients studied.