caa a22 4500 467932409 CHVBK 20180406152947.0 cr unu---uuuuu 170328e20060201xx s 000 0 eng 10.1007/s10545-006-0208-0 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0208-0 Asymmetric dimethylarginine in homocystinuria due to cystathionine β-synthase deficiency: Relevance of renal function [Elektronische Daten] [David Wilcken, Jun Wang, Ah Sim, Kathryn Green, Bridget Wilcken] Summary: Objective Vascular disease is associated with increased plasma asymmetric dimethylarginine (ADMA) and homocysteine, and both are increased in renal failure. In cystathionine β-synthase deficiency (CBS) there is severe hyperhomocysteinaemia, precocious vascular disease, and endothelial dysfunction. We investigated whether ADMA levels are elevated in CBS patients with and without renal impairment, and whether lowering plasma homocysteine also lowers ADMA. Methods We measured plasma homocysteine, arginine, asymmetric and symmetric dimethylarginines, nitrate + nitrite, creatinine and cystatin C in 23 CBS-deficient patients and 24 age-matched controls. Results In the patients, nitrate + nitrite and the ratio L-arginine/ADMA were markedly reduced (21.6 ± 6.1 vs 57.7 ± 7.5 μmol/L and 132.9 ± 24.7 vs 181.9 ± 56.1, respectively, p < 0.001 for both), reflecting endothelial dysfunction. Plasma ADMA for the group was moderately increased (0.55 ± 0.08 vs 0.49 ± 0.07 μmol/L, p = 0.018), but this was due to significantly higher levels than controls in only those 7 of the 23 patients who had elevated cystatin C levels (0.59 ± 0.08 vs 0.49 ± 0.07 mg/L, p = 0.007). Posttreatment total homocysteine in patients varied widely (15-285, median 92 μmol/L), but was not correlated with ADMA or other measured variables. In three newly-diagnosed patients, marked reduction of total homocysteine during treatment produced minimal changes in ADMA. Conclusions ADMA levels were significantly increased only in the CBS-deficient patients with elevated cystatin C levels, and not in those with normal renal function. The reported relationship between hyperhomocysteinaemia and ADMA may not be direct, but could be secondary to reduced renal function. SSIEM and Springer, 2006 Wilcken David University of New South Wales, Sydney, Australia aut Wang Jun The Prince of Wales Hospital, Sydney, Australia aut Sim Ah The Prince of Wales Hospital, Sydney, Australia aut Green Kathryn Children's Hospital at Westmead, Sydney, Australia aut Wilcken Bridget The University of Sydney, Sydney, Australia aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 30-37 0141-8955 29:1<30 2006 29 10545 https://doi.org/10.1007/s10545-006-0208-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0208-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wilcken David University of New South Wales, Sydney, Australia aut NATIONALLICENCE 700 1- Wang Jun The Prince of Wales Hospital, Sydney, Australia aut NATIONALLICENCE 700 1- Sim Ah The Prince of Wales Hospital, Sydney, Australia aut NATIONALLICENCE 700 1- Green Kathryn Children's Hospital at Westmead, Sydney, Australia aut NATIONALLICENCE 700 1- Wilcken Bridget The University of Sydney, Sydney, Australia aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 30-37 0141-8955 29:1<30 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer