ABSTRACT
Homocystinuria (HCU) due to cystathionine β-synthase (CBS) deficiency leads 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 time 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 treatment on the vascular outcome of a total of 84 patients with 1314 patient-years
of treatment for HCU. The mean (range) age was 27.8 (2.5 to 70) years. Five VE were
recorded during treatment; one pulmonary embolism, two myocardial infarctions, and
two abdominal aneurysms. All five VE occurred in B
6 -responsive patients at a mean (range) age of 48.8 (30 to 60) years. In 1314 patient-years
of treatment, 53 VE would have been expected if they remained untreated; instead only
5 were documented, relative risk = 0.091 (95% confidence interval [CI] 0.043 to 0.190;
p < 0.001). Appropriate homocysteine-lowering therapy for severe HHcy significantly
reduced the vascular risk in patients with HCU. VE were rare with treatment despite
the fact that the post-treatment homocysteine levels 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 vascular
disease, with elevated plasma homocysteine levels considerably lower than that of
the post-treatment levels in this group of reported patients.
KEYWORD
Homocystinuria - cystathionine β-synthase deficiency - severe hyperhomocysteinemia
- vascular complications - effects of treatment
