title: Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease.
abstract: BACKGROUND
  Fabry disease (FD) is a rare disorder and one of the causes of progressive renal and cardiac dysfunction. FD results from an X-linked recessive lysosomal storage disorder caused by a defect in the gene encoding lysosomal α-galactosidase A. Although accumulation of globotriaosylceramide leads to renal and cardiac manifestations, the precise mechanisms remain unclear. Coronary microvascular dysfunction may be one of the causes of cardiac complications in FD. We aimed to assess coronary flow reserve (CFR) and the effect of enzyme replacement therapy (ERT) on coronary microvascular dysfunction.
  
  
  METHODS
  Four FD patients who had never received ERT were included. The serum asymmetric dimethylarginine (ADMA) level, as a marker of endothelial dysfunction, was measured. Two-dimensional guided M-mode echocardiography was performed to measure left ventricular wall mass. Adenosine-triphosphate stress transthoracic Doppler echocardiography was used to measure CFR before starting ERT and at 3, 6 and 12 months.
  
  
  RESULTS
  All the patients tolerated ERT without any side effects. At the baseline, two patients had impaired CFR, increased left ventricular mass index (LVMI) and elevated serum ADMA levels. Twelve months after starting ERT, CFR was increased in all patients, and LVMI and serum ADMA levels decreased in two patients. Furthermore, serum ADMA levels significantly correlated with CFR (r= -0.576, P < 0.05) and LVMI (r= 0.874, P < 0.0001).
  
  
  CONCLUSIONS
  The results suggest that ERT prevented the progression of cardiac abnormalities, possibly by improving coronary microvascular dysfunction. ADMA may be a useful surrogate marker in FD.
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Hideki
authors: H
authors: Fujii
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Keiji
authors: K
authors: Kono
authors: Department of Clinical Laboratory , Kobe University Hospital , Kobe , Japan.
authors: Tetsushi
authors: T
authors: Yamamoto
authors: Division of Cardiovascular Medicine , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Tetsuari
authors: T
authors: Onishi
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Shunsuke
authors: S
authors: Goto
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Kentaro
authors: K
authors: Nakai
authors: Division of Cardiovascular Medicine , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Hiroya
authors: H
authors: Kawai
authors: Division of Cardiovascular Medicine , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Ken-Ichi
authors: KI
authors: Hirata
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan ; Division of Nephrology and Metabolism, Department of Internal Medicine , Tokai University School of Medicine , Isehara , Japan.
authors: Masafumi
authors: M
authors: Fukagawa
authors: Division of Nephrology and Kidney Center , Kobe University Graduate School of Medicine , Kobe , Japan.
authors: Shinichi
authors: S
authors: Nishi
keywords: Fabry disease; asymmetric dimethylarginine; coronary flow reserve; enzyme replacement therapy; left ventricular mass index