Pulse of Longwood takes you inside one of the nation’s largest hubs of hospitals and biomedical research.

Five-year-old LamLam Guo has spent most of his life in hospitals. Since he was a baby, he has suffered from weak muscles and has had trouble eating, but doctors can’t explain why. He lies in a hospital bed in Hong Kong, wrapped in a blanket, unable to move his eyes or to breathe on his own.

His story, spread widely on Chinese social media, has caught the attention of geneticists from England, China, and across the United States. Scientists from academic and commercial groups are now volunteering their time to find the genetic cause of Guo’s disease, seeking to help a heartbroken family — and to try to demonstrate the power of genome sequencing to a Chinese audience.

advertisement

An international team of 16 scientists — including from Boston Children’s Hospital, Baylor College of Medicine, Johns Hopkins University, and several commercial enterprises and Chinese universities — now discuss the case daily in a private group on WeChat, a messaging service in China that boasts 650 million active users per month. Guo’s parents have opened up the family’s genetic information, and Guo’s full medical file, to those who are willing to help.

It’s one of many collective, Web-based efforts that are cropping up around the world to help families of children with rare diseases find diagnoses. Through the Web, scientists can look at the same DNA sequence, conduct their own analyses, and easily compare notes. Companies are seeing a burgeoning market as more families look to the genome for answers. But families’ hope is tempered by discouraging odds: For two-thirds of families, genetic sequencing does not lead to diagnosis, according to the Undiagnosed Diseases Network.

Guo’s story begins on Dec. 11, 2009, in Hong Kong, when Sarina Lee and Suqiang Guo gave birth to their first child. At first, he seemed normal, Lee recalled in a recent Skype interview from her son’s Hong Kong hospital room.

But problems soon developed. Guo had trouble feeding. He would vomit and choke. He kept getting pneumonia. His muscles were very weak.

Lee, a financial planner, said she took Guo to private hospitals, to famous pediatricians in Hong Kong, and to mainland China, but no one could explain her son’s condition. She has gone to great lengths to care for him, at one point spending hours on trains between Hong Kong and Shenzhen every day to see her son at a hospital before and after work.

In 2012, the couple had a second child, QianQian Guo.

“Everyone felt QianQian would be a normal kid,” Lee said through a translator.

Dr. Yiping Shen is one of many scientists worldwide trying to help a Chinese family figure out the basis of their son's undiagnosed genetic disorder.
Yiping Shen is one of many scientists worldwide trying to help a Chinese family figure out the basis of their son’s undiagnosed genetic disorder. Jessica Rinaldi/The Boston Globe

But the girl developed problems feeding, too. And like her brother, her muscles were very weak.

Home videos show some of the family’s happier moments. In one clip, QianQian Guo smiles and plays with a plastic watermelon. In another, Guo pats his baby sister on her belly. They play in the park together. He pushes her stroller in the mall.

It was never clear if they suffered from the same disorder, Lee said.

QianQian Guo remained undiagnosed and her condition deteriorated. In December 2013, shortly after recovering from a viral infection that enlarged her heart, QianQian Guo died in her sleep of heart failure.

The loss rocked the family. Guo’s grandmother stopped coming to Hong Kong to visit him because QianQian Guo’s death was too painful to bear. QianQian Guo’s death intensified her parents’ quest to find help for their son.

The family’s medical odyssey is not unique: It takes over seven years on average to reach a correct diagnosis of a rare disease in the United States, according to one survey. While worldwide estimates are tough to pin down, about 25 million people in the US have a rare disease — defined as affecting fewer than 200,000 Americans. More parents are turning to the Web to find diagnoses through collective brainpower — though they are not all as successful in drawing attention as Guo’s family has been.

In August of this year, Lee and her husband turned to social media for help. Through connections at Tsinghua University, a research university in Beijing, they got an alumni group to post a plea for help on WeChat. 

“A child with an undiagnosed rare disease for five years: Tsinghua alumni seeking help to find the cause!” the message read. It went viral, reaching 148,000 people in six days, according to Yiping Shen, a geneticist at Boston Children’s Hospital who has become heavily involved in the case.

Just two days after the plea hit WeChat, Tsinghua University, Hong Kong University, Fu Wai Hospital in Beijing, and the University of Southern California all volunteered to offer genetic sequencing, Shen said. Three groups did DNA sequencing for the family. Still more scientists are analyzing the data, and discussing their findings in the WeChat group.

On a recent morning, Shen presented the latest findings to a new audience: 50 scientists and doctors in a carpeted conference room at Boston’s Brigham and Women’s Hospital. The occasion was the Genomic Medicine Case Conference, a monthly gathering of Boston geneticists who help each other solve tough cases like this one.

Shen, who is from China, presented LamLam Guo’s case, complete with family photos and videos. As medical director of clinical genetics at Claritas Genomics, a Boston Children’s Hospital spin-off company, Shen has been working with Wuxi NextCode, a genetic analysis company with offices in Shanghai and Cambridge, Mass., to examine the genomes of LamLam Guo and his sister and parents.

Dr. Yiping Shen points to a recent photograph of a Chinese child who is fighting an undiagnosed genetic disorder on his computer screen inside his office in Cambridge, Mass.
Yiping Shen points to a recent photograph of a Chinese child who is fighting an undiagnosed genetic disorder on his computer screen inside his office in Cambridge, Mass. Jessica Rinaldi/The Boston Globe

The prime suspect in LamLam Guo’s suffering, Shen said, is a gene called PFKM that is essential for the body’s conversion of sugar to energy. Other mutations in this gene have been linked to muscle weakness, but LamLam Guo has a mutation on that gene that has never been seen before. The mutation is unusual because it shows up in both children’s genomes but not in their parents’.

Shen believes that mutation might be causing LamLam Guo’s disease, but he has to prove it. The only way to do that, he said, is a functional study. Wuxi NextCode aims to create an enzyme that carries this mutation, and test whether that mutant enzyme shows abnormal function in converting one form of sugar to another.

At the same time, LamLam Guo’s family is trying out one treatment that emerged from the Brigham brainstorming session: daily doses of fructose. It may sound too simple to cure a kid who has been suffering all of his life. But why not try? Doctors in Hong Kong have started giving LamLam measured doses of apple juice to see if that helps.

If scientists determine his troubles are indeed caused by PFKM, that may open the door to finding more kids with the same mutation and experimenting with other treatments. But for the vast majority of rare diseases there are still no treatments, according to the National Institutes of Health.

Meanwhile, Lee has been spending four nights a week sleeping in a small cot next to her son’s hospital bed. At 11 pm one recent weeknight, she turned on her cell phone camera and showed her son, asleep on his bed in a pink hospital gown. Lee said she is anxious to learn the genetic basis of her son’s illness, in part because she is under family pressure to have another child. She said the attention from international experts has given her some hope.

“God has opened a window for this tough time in life.”

Leave a Comment

Please enter your name.
Please enter a comment.

Sign up for our Morning Rounds newsletter

Your daily dose of news in health and medicine.

X