Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy.
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.
Stanger
Olaf
O
Department of Cardiac Surgery, Atherosclerosis Research, Paracelsus Medical University, Salzburg, Austria. o.stanger@salk.at
Weger
Martin
M
Obeid
Rima
R
Temmel
Werner
W
Meinitzer
Andreas
A
Steinbrugger
Iris
I
Schmut
Otto
O
Herrmann
Wolfgang
W
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009901:Optic Nerve Diseases / Q000378:metabolism*; D012170:Retinal Vein Occlusion / Q000378:metabolism*
D006710:Homocysteine