Discovery of New Rare Disease Involving Inability to Process B-12 Found in Colorado Boy

September 19, 2013

Researchers from the University of Colorado School of Medicine and Children’s Hospital Colorado announced Thursday they had solved the riddle of Max’s metabolic disorder and discovered a new genetic disease. Their findings were published Thursday in the American Journal of Human Genetics.

The bittersweet news for Max and his family is that his genes have made a major contribution to science, even as those genes have failed him. The researchers say identifying Max’s genetic mutation could help create a treatment in years to come, but there is no reversing his rare condition.

“Many of the bad things that were going to happen to Max already happened when he was still in utero,” said CU geneticist Tamim Shaikh, lead author of the journal article about the new disease.

The Watson family was glad to know that years of frustration had a deeper meaning.

“The next time a child is born with this disease, they will know right then, not four months down the line when the damage has already happened to the body and the brain,” said Max’s mother, Deana. “Maybe further down the line, they’ll find a cure, so it’s not a worry for any family ever.”

Max Watson was born with symptoms mimicking previously known metabolic problems, stemming from his body’s inability to properly use the key vitamin B-12. His cells couldn’t convert the dairy-eggs-and-meat vitamin into an important amino acid, and he suffered seizures, anemia and severe vomiting. He eventually needed brain surgery to remove portions causing the seizures.

CU doctors and researchers starting seeing Max at only a few months old, prodding with genetic and metabolic tests. His disorder looked like a known cobalamin (B-12) deficiency, but he and his parents did not have the genetic mutation that caused the disease in previous cases.

In the meantime, doctors were preventing further damage by giving Max B-12 in forms that he could absorb. But the Watsons had no idea of a root cause or whether they should warn relatives about possible genetic flaws running in the family.

Max, who uses a wheelchair, worked his way up to fourth grade in Westminster with video conferences to his classrooms, and teacher visits supplied by the district. He doesn’t write or speak, but uses categories and letters on his talking computer to create sentences.

For a report on heroes, he chose Martin Luther King Jr. and how he strived for equality.

At 4 feet 10 inches and 80 pounds, Max is a lanky handful, often lifted from place to place by his father, Steve. His parents take him to outdoor sights, like the Botanic Gardens, since indoor crowds can make him sick— a stomach bug can put him in the ICU for a week and take a month to shake entirely.

“So eight years in, I came into it, and he’s already been tested for every imaginable thing,” said Shaikh, who acts as an analyst of inscrutable cases at CU’s Anschutz Medical Campus.

Computing power and the Human Genome Project have allowed scientists to more cheaply look at thousands of a patient’s genes at once, rather than one at a time. A $1,000 look at Max’s genome told Shaikh’s team the answer: he had a mutation on one X chromosome.

Max’s mom had it, too, but females with a second X chromosome have a “backup” X gene that can cover for such a flaw.

“He was dealt a bad hand genetically,” Shaikh said. So far, the team has found Max’s flaw only 13 other times in samples from around the world.

That always comes as a relief to families, who don’t have to agonize over something they did wrong. Deana Watson collected samples from her side of the family and learned she was the only one with the mutation.

“It was really interesting to watch as I told my family members that it didn’t come from you, or you, or you,” she said. “You could just see the relief on their face because no one wants to pass on such a devastating disease to someone. There was just always that question: Where did it come from and whose side did it come from?”

Along the way, the Watsons have learned that Max the human is teaching the researchers as much as they are learning from Max the collection of genes.

A few years ago, they took Max to a National Institutes of Health investigator.

“They looked at (his) blood and heart and metabolics and brain, but they hadn’t talked about his ability,” Steve Watson said.

Deana took out Max’s speaking device and started asking him questions. He knew what state they were in, the color of his shirt, the name of his disease and the names of his doctors.

The head researcher scooted back and put his head in his hands for a few minutes.

“When he’d composed himself,” Steve said, “he asked ‘How many kids, for how many years, had something going on in their head and we never knew?’ ”

Read more at The Denver Post.

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