Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: Effects of homocysteine-lowering therapy

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency le ads to severe hyperhomocysteinemia (HHcy). Vascular events (VE) remain the major cause of morbidity and mortality in the untreated patients with HCU. The study on the natural history of untreated HCU disclosed that, at the ti me of maximal risk, in other words beyond 10 years old, there was one event per 25 years. Recent studies from Australia (n = 32), The Netherlands (n = 28), and Ireland (n = 24) have documented the effects of long-term treatme nt on the vascular outcome of a total of 84 patients with 1314 patient-year s of treatment for HCU. The mean (range) age was 27.8 (2.5 to 70) years. Fi ve VE were recorded during treatment; one pulmonary embolism, two myocardia l infarctions, and two abdominal aneurysms. All five VE occurred in B-6-res ponsive patients at a mean (range) age of 48.8 (30 to 60) years. In 1314 pa tient-years of treatment, 53 VE would have been expected if they remained u ntreated; instead only 5 were documented, relative risk = 0.091 (95% confid ence interval [CI] 0.043 to 0.190; p < 0.001). Appropriate homocysteine-low ering therapy for severe III-Icy significantly reduced the vascular risk in patients with HCU. VE were rare with treatment despite the fact that the p ost-treatment homocysteine Bevels were several times higher than the cutoff point for Homocysteine in the normal population. The present findings may have relevance to the current concept of "mild HHcy" as a risk factor for v ascular disease, with elevated plasma homocysteine levels considerably lowe r than that of the post-treatment levels in this group of reported patients .