Childrens behavior

Lifetime mission: State to use Dr Sihoun Hahn’s newborn screening test for Wilson disease

Kaitlyn and Ryan Wyckoff travel from their hometown of Wasilla, Alaska to Seattle Children’s so that Dr. Sihoun Hahn (center) can monitor and treat them for Wilson’s disease, a rare genetic disorder.

The lifetime goal of Dr Sihoun Hahn, director of the Wilson Disease Center of Excellence and researcher at Seattle Children’s Research Institute’s Center for Integrative Brain Research, is one more step towards realization.

After more than 30 years of studying Wilson’s disease, Hahn’s newborn screening test for this rare genetic disorder will be tested in a pilot study by the Washington State Department of Health by the end of this year. the year. If the study is successful, Hahn’s test could soon be used to diagnose infants across the country with the deadly, but easily treatable disease.

Wilson’s disease is a genetic disease that causes excess copper to build up in the body. Although copper build-up begins at birth, symptoms do not appear until late childhood or early adolescence. At this stage, patients often have severe and permanent effects, including liver failure or neurological deterioration.

Additionally, one-third of people with Wilson’s disease experience psychiatric symptoms, such as sudden personality changes and inappropriate behavior, depression, neurosis, or psychosis.

Susan Takemoto’s daughter Julia was accidentally diagnosed with Wilson’s disease at the age of 6. She had been sicker than usual, so her pediatrician ordered a routine blood test which showed unusually high liver enzymes. A subsequent biopsy at Seattle Children’s revealed scar tissue in Julia’s liver, which led to a diagnosis of Wilson’s disease.

Julia is now 21 years old. Because her disease was detected early, she was able to lead a healthy lifestyle with simple daily zinc treatments.

Not all patients are so fortunate. Ryan Wyckoff, of Wasilla, Alaska, was 15 when he fell seriously ill for the first time in his life. He was lethargic and had an uncontrollable high fever. He gained 15 pounds in two days from the fluid filling his abdomen.

“It’s terrifying to have something really wrong with your son that nobody can figure out,” said Lisa, Ryan’s mom. “We felt so helpless.”

An MRI scan revealed Ryan had advanced and potentially fatal scars in his liver. He was airlifted to Seattle Children’s via medevac and later diagnosed with Wilson’s disease.

Decades spent searching

Hahn began caring for Wilson’s disease patients as a member of the National Institutes of Health in 1990. Although the disease is rare – affecting approximately 150 newborns in the United States each year – patients treated with Hahn left a lasting impression on him.

“It was very sad,” Hahn said. “These children seemed perfectly healthy and then suddenly they deteriorated rapidly. Many had permanent brain damage or needed a liver transplant. Some had tremors, slurred speech, or could not walk or swallow.

Hahn began to study the molecular biology of Wilson’s disease and found that the disease was caused by a genetic defect in the ATP7B gene. While this helped to better understand the disease, patients were still only diagnosed after developing significant effects.

Hahn realized that the best way to help children with Wilson’s disease was to find it early. It was then that he began to focus his research on developing a newborn screening.

For 20 years, Hahn searched for a gene or protein that could be used to reliably identify Wilson’s disease. He first developed a test that identified ceruloplasmin, a protein made in the liver that carries copper into the bloodstream. But after screening thousands of newborns, Hahn realized that the test had given too many false positive results.

“To be a leader in a field, you have to continue to look to the future. It’s Dr Hahn. He has a vision of the value of this exciting work to his patients and their families for future generations. I am very excited to see how his test works.

Dr Michael Schilsky, President of Wilson Disease Association Medical Advisory Committee, has occasionally collaborated with Sihoun during his years of research.

Yet Hahn persevered.

“I didn’t want to give up,” Hahn said. “It was my life’s mission. I was fortunate to have the support of the Seattle Children’s Research Institute and the NIH to be able to continue.

Hahn knew Wilson’s disease was caused by mutations in the ATP7B gene. His team therefore developed a method for measuring ATP7B in dried blood stains from heel pricks in newborns.

The ATP7B screening test turned out to be correct, but Hahn needed to build commercial test kits before they could be tested. With community support, Hahn has created a start-up to build test kits that will be used by the Washington state newborn screening lab in a pilot study to be launched later this year.

Washington State is about to launch a pilot study to screen 75,000 newborns using a test developed by Dr. Hahn. If successful, the test could ultimately be used to screen newborns across the country for this deadly, but easily treatable disease.

Hahn expects the study to lead to Food and Drug Administration approval, after which he will request that the Wilson disease test be included in the nationally recommended newborn screening panel so that infants across the country are tested before symptoms appear.

If approved, Hahn’s screening method could also be used to diagnose at least three other primary immunodeficiencies for which newborns are not currently tested – X-linked agammaglobulinemia, Wiskott-Aldrich syndrome and Adenosine deaminase deficiency.

“If diagnosed early, each of these conditions can be treated effectively and children can continue to live normal, healthy lives,” Hahn said.

In support of research

Lisa knows how important early detection is. Although Ryan was diagnosed within 48 hours of arriving at the Children’s, he already had permanent liver damage. He quickly began treatment with Syprine, a chelating agent that removes copper from the body. Years later, Ryan’s cirrhosis caused his spleen to swell, requiring urgent life-threatening surgery to remove it.

“Working with Dr Hahn has been like watching the light shine through rain clouds. He is so determined to make this disease a bearable disease; it gives us hope.

– Susan Takemoto, Julia’s mother

“Ryan wouldn’t have suffered as much damage to his organs if we had found out about his illness earlier,” Lisa said. “I think every time he ate foods rich in copper like chocolate or a peanut butter sandwich. These things were terrible for him, but we had no idea.

Ryan and Julia, along with their asymptomatic siblings who also tested positive for Wilson’s disease, provided blood samples for Hahn’s research.

“I understand Wilson’s disease is rare,” Lisa said. “But if newborn screening could prevent a single child from having to deal with the trauma my son experienced, then we will do all we can to help him.”

After 30 years, Hahn’s dedication to this research has only grown. “I would like to retire soon,” he said. “But not until we have national screening for Wilson’s disease.”

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