麻豆果冻传媒

For Release: May 12, 2010

PALO ALTO, Calif.聽- As he was being born at Lucile Packard Children鈥檚 Hospital Stanford, Dean Thao received infusions of a medication 鈥� never before given prenatally 鈥� for a rare metabolic defect that usually causes permanent brain damage, and often death. Thanks to聽medical geneticists聽at the hospital who identified the defect at 34 weeks gestation, the doctors were prepared to begin treatment at labor and continued to guard and treat his condition over the next three months until, on March 8, he could get a new liver.

Ornithine transcarbamylase, or OTC, deficiency, is a genetic disorder that appears in one in 40,000 births. Because of a genetic defect, the body鈥檚 metabolic machinery is jammed, with the liver failing to function properly. The result can be sudden spikes of ammonia, from normally small amounts naturally occurring in the body to levels that are toxic. Although the disease has its primary metabolic effect in the liver, it is the brain that bears the brunt of OTC deficiency. Doctors have rescued children with OTC deficiency and other metabolic disorders before by using specialized medicine infusions, intensive nutritional support, and liver transplantation. Indeed, Enns, who is also associate professor of pediatrics in the Division of Medical Genetics at Stanford University School of Medicine, has worked with Packard Children鈥檚聽pediatric liver transplant team聽to treat eight children with OTC deficiency at the hospital.

But often by the time Enns and others intervened after birth, the children鈥檚 brains had suffered damage. More than half of kids surviving OTC deficiency crises have brain damage, and about 80 percent have developmental issues, Enns said. 鈥淭he neurological outcome is typically very poor,鈥� he noted. 鈥淲e have a number of children with urea cycle disorders with normal intelligence, but often the damage is already done at the time of diagnosis, since these disorders are so severe and strike so quickly.鈥�

At Risk

Shoua Yang came to Packard Children鈥檚 worried she had a fetus at risk. Her own mother had lost two sons, though no one had attributed those deaths to genetics. When Yang lost her own firstborn son 10 years ago, she was told the cause was an OTC deficiency. But it was easier back then to leave it as 鈥淕od鈥檚 will,鈥� she said, than to acknowledge the gene defect. She went on to have two daughters and a son, all healthy. When Yang became pregnant last year with Dean, midwife Renee Halstead, MD, of Women鈥檚 Specialty Center in Clovis, CA, urged her to get the amniocentesis. 鈥淒r. Halstead was hard to say no to,鈥� said Yang. 鈥淪he pushed me to get tested. Now, I am so thankful.鈥�

鈥淎nd I needed to find out,鈥� she added, 鈥渇or my girls.鈥� The disorder is caused by a defect on the X chromosome. What that means is that OTC deficiency fully affects only boys, as males have only one X chromosome. In girls, with two X chromosomes, the normal one can compensate for the bad one. Her daughters could be carriers. But the vital question was whether Yang was passing the OTC gene to this new son. 鈥漁ur prenatal and biochemical genetics team is among a select group nationally that has the expertise to identify and care for OTC deficiency,鈥� said Enns. 鈥淲e had to sequence the gene in the mom, then look for it in the fetus.鈥� The particular mutation had to be found and sought in the fetal cells obtained. And indeed, the amnio showed it was there.

To prevent an ammonia spike during Yang鈥檚 labor on November 17, 2009, Enns and his colleagues put part one of their plan in motion, first infusing a solution of sodium phenylacetate and sodium benzoate, along with arginine hydrochloride, into Yang鈥檚 bloodstream to safely capture the toxin. These infusions help to 鈥榮cavenge鈥� excess ammonia in urea cycle disorder patients. This was the first time the combination of infusions was carried out during labor as far as we know, Enns said. After the birth, mom and baby stayed close to Packard Children鈥檚 at the聽聽to await a donor liver and transplant, which would effect the cure. Yang fed Dean a special low-protein formula and she watched for low body temperature or tiredness that could indicate another ammonia spike 鈥� he had a mild one in December that was treated quickly in the hospital鈥檚聽Neonatal Intensive Care Unit.

On March 8, Yang was told that a matching liver for Dean was available.聽Carlos Esquivel, MD, PhD, director of transplantation, led the surgical team in a four-hour procedure.聽 According to medical literature, Enns said, this makes Dean the first documented infant with OTC deficiency to undergo a聽liver transplant聽after continuous treatment with this combination of medications and monitoring from before birth. Now, with regular outpatient visits to clinics at Packard Children鈥檚 to check Dean鈥檚 progress, Yang and her growing boy are looking to the future and what will hopefully be a normal life back home with his sisters and brother. 鈥淲e are looking forward to the happy days ahead,鈥� said Yang.

Dean鈥檚 experience is definitely a new standard of care, 鈥渂ut only specialized institutions are able to do this,鈥� said Enns. 鈥淵ou need the experience. It鈥檚 setting the bar high, but it does set a goal in place.鈥� 鈥淥ur whole focus was to provide treatment that would keep his brain healthy, and so far things are looking great,鈥� said Enns, who plans to publish the case. 鈥淭hough Dean will always need medications to help avoid transplant rejection and there may be other issues, he now has an excellent chance at a full, active life.鈥�

Authors

Robert Dicks
(650) 497-8364
rdicks@stanfordchildrens.org