The effectiveness of sodium phenylacetate and sodium benzoate, two chemicals the body already makes to carry nitrogen for disposal in urine "just knocked my socks off from the moment we first tried them," recalls Saul Brusilow, M.D., professor emeritus of pediatrics at Hopkins who first had the notion to use the drugs. "In all my years I never came across another disease where patients come in near-comatose and you stick a needle in them and lo and behold, they wake up—just like that. It was just astonishing," he says.
"His elegant idea was to give patients chemicals they already make in small amounts in large doses to make up for the missing urea cycle enzyme they inherited," says Ada Hamosh, M.D., M.P.H, clinical director of the McKusick-Nathans Institute of Genetic Medicine. "Sodium phenylacetate and sodium benzoate already know how to eliminate nitrogen in urine, so having more in the body carries more nitrogen out and reduces the toxic effects of excess nitrogen accumulation."
Excess nitrogen yields ammonia, which is poisonous and in the case of urea cycle disorders, causes brain damage, retardation, coma and even death.
Despite the immediate clinical success of the treatment, the drug combination was finally approved by the U.S. Food and Drug Administration only in 2005.
Brusilow, Hamosh, and colleagues at Stanford University, University of Minnesota, Thomas Jefferson University and the Medical College of Wisconsin looked back at 299 urea cycle disorder patients with a total of 1,181 hyperammonemia "episodes" from 118 hospitals around the United States from August 1980 until March 2005.
The regimen consisted of high-dose intravenous sodium phenylacetate and sodium benzoate for two hours followed by "maintenance infusions" until blood ammonia levels were normal. The patients’ overall survival rate was 84 percent, and 96 percent survived episodes of severe ammonia poisoning.
An estimated one in 40,000 live births is a child with a urea cycle disorder, according to Hamosh, who says early and accurate detection can now assure prompt treatment.
"We’re teaching all medical students at Hopkins to consider hyperammonemia and immediately do blood tests when they see a combative, lethargic or comatose newborn or child," she says. "The longer the hyperammonemia lasts, the higher the risk for brain damage."
"This is a happy story," says Brusilow. "It isn’t too often in genetic medicine that we can intuitively develop a treatment with already available chemicals and save lives."
Audrey Huang | EurekAlert!
New findings help to better calculate the oceans’ contribution to climate regulation
14.11.2018 | Jacobs University Bremen gGmbH
How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration
14.11.2018 | Technische Universität München
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
14.11.2018 | Materials Sciences
14.11.2018 | Health and Medicine
14.11.2018 | Life Sciences