Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder

Summary

Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.

Timeline

Start

2008-02

Primary completion

2011-05

Completion

2012-11

Publications

• Background Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Van Beers BE. Hepatic flow parameters measured with MR imaging and Doppler US: correlations with degree of cirrhosis and portal hypertension. Radiology. 2003 Nov;229(2):409-14. doi: 10.1148/radiol.2292021128. Epub 2003 Sep 11.
• Background Lu LG, Zeng MD, Wan MB, Li CZ, Mao YM, Li JQ, Qiu DK, Cao AP, Ye J, Cai X, Chen CW, Wang JY, Wu SM, Zhu JS, Zhou XQ. Grading and staging of hepatic fibrosis, and its relationship with noninvasive diagnostic parameters. World J Gastroenterol. 2003 Nov;9(11):2574-8. doi: 10.3748/wjg.v9.i11.2574.
• Background Scaglia F, Marini J, Rosenberger J, Henry J, Garlick P, Lee B, Reeds P. Differential utilization of systemic and enteral ammonia for urea synthesis in control subjects and ornithine transcarbamylase deficiency carriers. Am J Clin Nutr. 2003 Oct;78(4):749-55. doi: 10.1093/ajcn/78.4.749.
• Background Lee B, Yu H, Jahoor F, O'Brien W, Beaudet AL, Reeds P. In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8021-6. doi: 10.1073/pnas.140082197.
• Background Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr. 1996;43:127-70. No abstract available.

Drugs

Indications