Mild
hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as
retinal vascular occlusion and non-arteritic
ischemic optic neuropathy (
NAION). Low intake or low status of
B-vitamins explains elevated total
homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed
homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy,
methylmalonic acid (MMA) and
cystathionine provide more information on the causes of impaired
homocysteine metabolism as compared with
vitamin B12,
vitamin B6 and
folate in patients with ocular ischemic
vascular disease. A total of 51 hyperhomocysteinemic (>12 micromol/L) patients with
retinal vascular occlusion (n=42) and
NAION (n=9) were included. Mild renal dysfunction was an important determinant of tHcy, indicated by the positive correlation between
creatinine and tHcy (r=0.47, p=0.001). The assessment of MMA in addition to tHcy identified at least 12 out of 51 patients (23%) who were most likely to have a functional
vitamin B12 deficiency. An additional 14 patients (27%) with elevated MMA and
cystathionine levels also had slightly elevated concentrations of
creatinine, pointing to the need for discrimination between renal dysfunction and
vitamin B12 deficiency in this group. In contrast, measurement of
cystathionine is very sensitive for renal dysfunction and this marker was strongly related to serum
creatinine (r=0.56, p<0.001) and to tHcy (r=0.50, p<0.001). Measurement of the
vitamins folate,
vitamin B12 and
vitamin B6 in plasma did not provide sufficient information on intracellular disturbances in
homocysteine metabolism. In conclusion, the metabolites
homocysteine,
cystathionine and MMA are sensitive indicators and valuable for discrimination of the underlying cause of mild to moderate
hyperhomocysteinemia, with implications for therapeutic targeting.