Journal
MOLECULAR GENETICS AND METABOLISM
Volume 107, Issue 3, Pages 315-321Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2012.09.016
Keywords
Rare disease clinical research; Argininosuccinate lyase; Argininosuccinic aciduria; Arginine therapy; Hepatic disease
Funding
- NIH Rare Diseases Clinical Research Network (RDCRN)
- National Institute of Child Health and Human Development 181 (NICHD) [U54HD061221]
- NIH Office of Rare Diseases Research (ORDR)
- NIH [DK54450, DK92921, RR19453, RR00188, GM90310, GM07526, DK081735, RR024173]
- Baylor College of Medicine General Clinical Research Center [RR00188]
- Intellectual and Developmental Disabilities Research Center [HD024064]
- Texas Medical Center Digestive Disease Center
- Urea Cycle Disorders Rare Disease Clinical Research Network, NIH [HD061221]
- National Urea Cycle Disorders Foundation Research Fellowship
- O'Malley Fellowship of the UCDC RDCRN
Ask authors/readers for more resources
Objective: To compare the effects of combinatorial therapy with low-dose arginine and a nitrogen scavenging agent (sodium phenylbutyrate) vs. monotherapy with high-dose arginine on liver function tests in patients with argininosuccinic aciduria (ASA). Study design: Twelve patients with ASA were enrolled in a double-blind, placebo-controlled, cross-over study design. Subjects were randomized to receive either a low-dose of arginine therapy (100 mg.kg(-1).d(-1)) combined with sodium phenylbutyrate (500 mg.kg(-1).d(-1)) (LDA arm) or a high-dose of arginine alone (500 mg.kg(-1).d(-1)) (HDA arm) for one week. At the end of one week of therapy, liver function tests were assessed and metabolite fluxes were measured using a multi-tracer stable isotope protocol. Results: Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and measures of synthetic functions of the liver were the primary outcomes. Subjects had significantly increased levels of argininosuccinate (P<0.03) and AST levels (P<0.01) after treatment with high-dose arginine. In the subset of subjects with elevated AST or ALT, treatment with high-dose of arginine was associated with further increases in plasma levels of both aminotransferases. Whereas subjects had increased arginine and citrulline flux with high-dose arginine therapy, the glutamine flux was not different between the two treatment arms. The synthetic liver functions as assessed by prothrombin time, INR, and coagulation factor levels were not different between the HDA and LDA arms. Conclusions: Administering higher doses of arginine in subjects with ASA results in increases in AST and ALT levels, especially in the subset of patients with elevated baseline aminotransferases. Hence, low-dose arginine sufficient to normalize arginine levels in plasma combined with nitrogen scavenging therapy should be considered as a therapeutic option for treatment of ASA in patients with elevations of hepatic aminotransferases. (C) 2012 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available