Journal of Inherited Metabolic Disease

, Volume 29, Issue 1, pp 30–37 | Cite as

Asymmetric dimethylarginine in homocystinuria due to cystathionine β-synthase deficiency: Relevance of renal function

  • David E. L. Wilcken
  • Jun Wang
  • Ah Siew Sim
  • Kathryn Green
  • Bridget Wilcken
Original Article


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.


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Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  • David E. L. Wilcken
    • 1
    • 2
  • Jun Wang
    • 3
  • Ah Siew Sim
    • 3
  • Kathryn Green
    • 5
  • Bridget Wilcken
    • 4
    • 5
  1. 1.University of New South WalesSydneyAustralia
  2. 2.The Professorial SuitePrince of Wales HospitalRandwick, SydneyAustralia
  3. 3.The Prince of Wales HospitalSydneyAustralia
  4. 4.The University of SydneySydneyAustralia
  5. 5.Children’s Hospital at WestmeadSydneyAustralia

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