Navigation Links
Once-Fatal Metabolic Disorders Treatable, Says Stanford/Packard,Researcher

STANFORD, Calif.--(BUSINESS WIRE)--May 30, 2007 - People with a class of rare genetic disorders that often lead to brain damage, coma and death can be successfully treated with drugs, says a researcher at the Stanford University School of Medicine and Lucile Packard Children's Hospital.

The researchers found in their unprecedented 25-year study that prompt diagnosis coupled with a rapid start of intravenous drug therapy significantly improves the survival rates of people with the condition, called urea cycle disorders. The condition affects proteins in the liver that are necessary to process the by-products of protein metabolism.

"Historically, the prognosis for patients with urea cycle disorders has been universally poor," said Gregory Enns, MD, director of the biochemical genetics program at Packard Children's. "To now be able to talk about the potential for normal outcomes is pretty remarkable."

Enns, who is also associate professor of pediatrics at Stanford's School of Medicine, collaborated with researchers from the Johns Hopkins School of Medicine, the University of Minnesota, Thomas Jefferson University and the Medical College of Wisconsin on the study, which will be published in the May 31 issue of The New England Journal of Medicine. Enns is the lead author of the study, and Hopkins researcher Ada Hamosh, MD, is the senior author.

Urea cycle disorders affect about one in every 8,200 people, but the diagnosis is often missed or delayed. The study took 25 years to accumulate enough patients to evaluate the drug treatment.

People with urea cycle disorders are unable to convert nitrogen-rich ammonia, a normal by-product of protein metabolism, into urea that is excreted by the body as urine. Mutations in several different proteins can short-circuit the urea cycle, which occurs in the liver, but the result is the same: escalating levels of blood nitrogen cause irreversible brain d amage, coma and death.

If a diagnosis is made quickly enough, dialysis can help to cleanse the blood of excess nitrogen during an episode and prevent brain damage.

Traditional treatments included maintaining a very-low protein diet that is still high enough in calories to avoid metabolizing any of the body's protein-rich muscle. Liver transplantation is also an option for some patients.

This study investigated whether drugs that promote alternative pathways to dismantle and excrete nitrogen-containing waste can lower the dangerously high levels of blood ammonia, called hyperammonemia.

The 299 people in the study experienced 1,181 episodes of hyperammonemia during the study period. Those who received the drug therapy had an overall survival rate of 73 percent for newborns and 98 percent for older patients. In contrast, a recent European study of 217 patients who did not receive the therapy reported overall survival rates of only 16 percent for newborns and 72 percent for people with later onset of disease.

Urea cycle disorders can become apparent at many different stages in life. Newborns with a complete blockage in the cycle begin to show symptoms within hours after birth but are often misdiagnosed. Older children or adults with less-severe mutations can lead normal lives until sickness or a change in diet overtax the body and bring on a life-threatening episode.

Only a fraction of the many possible mutations are picked up by expanded newborn screening, and precious days are lost while test results are processed. The lethargy, vomiting and rapid breathing exhibited by affected newborns are often misinterpreted and mistreated as hospital-acquired infections. "Newborn screening is good at detecting some urea cycle disorders, but we can't diagnose all of them this way," said Enns. "By the time the results come back, these kids are already in the hospital and going into a coma. The sooner you identify them, the better the possib le outcome."

Alternative pathway therapy includes a combination of two drugs that work to help the body rid itself of excess nitrogen: sodium phenylacetate and sodium benzoate. Metabolic disease expert Saul Brusilow, MD, at Johns Hopkins' Children's Center, pioneered the drug combination in the 1970s as a possible treatment for urea cycle disorders. Although early reports showed promising results, it took years to gather enough patients to prove the treatment's effectiveness.

Prompt treatment does more than just save lives, however. It also protects patients' brains and gives them a chance at a normal life.

"Traditionally, the cognitive outcome of these disorders has been horrible," said Enns. "There were ethical arguments to be made about even trying to help these kids. The rationale was 'Why treat if you're going to be left with a child who can't do anything?' Now we've shown that we can save these kids."

He added, "Although there are still significant hurdles to overcome--in particular, timely diagnosis--at least we know that normal intelligence is possible. All is not lost when a family gets this diagnosis."

The study was supported by grants from the General Clinical Research Centers at Johns Hopkins University, Children's Hospital of Philadelphia, and Children's National Medical Center; grants from the National Institute of Child Health and Human Development, the Food and Drug Administration, the National Center for Research Resources, and through support of the national General Clinical Research Network.

Sodium phenylacetate and sodium benzoate are marketed for the treatment of urea cycle disorders by Ucyclyd Pharma under the trade name Ammonul. Enns has received a lecture fee from Ucyclyd Pharma and a consulting fee from Ucyclyd Pharma for service at one meeting of the advisory board of the company.

Stanford University Medical Center integrates research, medical education and patient care at its three instituti ons -- Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.

Ranked as one of the best pediatric hospitals in the nation by U.S.News & World Report and Child magazine, Lucile Packard Children's Hospital at Stanford is a 264-bed hospital devoted to the care of children and expectant mothers. Providing pediatric and obstetric medical and surgical services and associated with the Stanford University School of Medicine, Packard Children's offers patients locally, regionally and nationally the full range of health care programs and services -- from preventive and routine care to the diagnosis and treatment of serious illness and injury. For more information, visit http://www.lpch.org.

Contact

Stanford University Medical Center
Print Media:
Krista Conger, 650-725-5371
kristac@stanford.edu
or
Broadcast Media:
Robert Dicks, 650-497-8364
rdicks@lpch.org


'"/>




Related medicine technology :

1. Lipitor Provides Unprecedented Cardiovascular Risk Reductions in Diabetes Patients with Metabolic Syndrome and in Stroke Patients
2. Study Presented at the ACC Shows Inflammatory Enzyme Lp-PLA2 Predicts Heart Disease Risk in Metabolic Syndrome Patients
3. Study Shows Metabolic Strategy of Stressed Cell
4. IMPAX Presents at Movement Disorder Societys 11th International Congress of Parkinsons Disease and Movement Disorders
5. Faust Pharmaceuticals Phase IIa Results for Parkinsons Disease Presented at International Congress of Parkinsons Disease and Movement Disorders
6. Cogane Data Presented at ‘11th International Congress of Parkinson’s Disease and Disorders’
7. Targeting Specific Mutations Reveals Promising New Approach to Treating Genetic Disorders; Preclinical Data Published in Nature
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... , March 23, 2017 The key ... population, increasing diabetic population, accelerating economic growth and increasing healthcare ... industry are higher life expectancy of ESRD patients, rising demand ... markets. However, the expansion of the market is hindered by ... ...
(Date:3/23/2017)... N.C. , March 23, 2017  Transportation Insight, ... as an end-to-end supply chain management firm with expertise ... Consumer Product Solutions Rick Zaffarano was named ... of the Supply Chain by the only publication exclusively ... global food supply chain. "Rick has brought ...
(Date:3/23/2017)... and INDIANAPOLIS , March 23, 2017 ... ) and the William Sansum Diabetes Center have established ... people affected by diabetes through enhanced research, education and ... and cardiovascular disease bears a disproportionate weight on Latino ... said David Kerr , M.D., FRCPE, director of ...
Breaking Medicine Technology:
(Date:3/24/2017)... ... March 24, 2017 , ... According to a new study ... because it does not obey the rules Congress has directed the CBO to follow. ... the GOP reform would restore. Yet, it estimates a reduction in employer-based coverage due ...
(Date:3/24/2017)... ... March 24, 2017 , ... The iaedp Foundation, the premier provider of educational ... those suffering from the full spectrum of disordered eating, announced today that the 2017 ... nearly all 50 states and several countries converged on the Green Valley Resort in ...
(Date:3/24/2017)... ... March 24, 2017 , ... Shamanic healer ... for Shamanic Healing and Spiritual Awakening, proudly presents her Sacred Peru retreat ... This sacred and spiritual journey during the Summer Solstice will also be her ...
(Date:3/24/2017)... PA (PRWEB) , ... March 24, 2017 , ... ... Oncology Nursing Society (ONS) wanted to create a communications platform that positions them ... this goal, Elliance and ONS reinvented their online publication as an always-on, always-fresh ...
(Date:3/24/2017)... (PRWEB) , ... March 24, 2017 , ... ... two panels at the Advanced ERISA Benefit Claims Litigation seminar in Chicago, Illinois. ... the Administrative Record, The majority of cases litigated under ERISA involve claims for ...
Breaking Medicine News(10 mins):