Genetics provide hope for rare diseases

Above: Riding and reaching for a toy help Asher Cohen, 4, who has alternating hemiplegia of childhood, improve his balance. Right: Asher and Nationwide Children’s occupational therapist Olivia Hazen.

Asher Cohen’s birth and first few months of life hinted at nothing out of the ordinary. He ate great, slept well and prompted little concern for first-time mom, Cate.

Then, when he was 3 months old, something strange happened. During a bath, Asher bent backward and stayed there, stiff, in a banana shape. His right eye appeared to have a tic of some sort and wasn’t focused on his mom. His left eye remained on Mrs. Cohen.

“Then he was fine,” the Northeast Side woman said, as she and her husband, Tobe, recalled the first signs of trouble for their now 4- year-old son.

He continued to have similar episodes, and doctors looked for evidence of disease in his brain or bone marrow. Finding nothing, they told the Cohens their son must have epilepsy.

Every 10 days to two weeks, Asher would have an episode; when he was 8 months old, doctors determined they were not seizures.

Without any answers, the Cohens hoped for the best. When their son crawled, he would sometimes drag his arm and struggle to balance. When he was 15 months old, he still wouldn’t let go of furniture and other props and walk on his own.

Eventually, a physical therapist mentioned a disease called “alternating hemiplegia of childhood,” or AHC. An estimated 1 in 1 million babies is born with it. Besides paralysis, patients have neurological and developmental problems.

When Asher was 2, a specialist in Chicago confirmed the diagnosis.

About 30 million Americans have rare diseases, those that affect fewer than 200,000 people in the U.S. at any given time, according to the National Organization for Rare Disorders. Because so few people have the diseases, researchers have often struggled to find conclusive explanations, and pharmaceutical companies have had limited incentive to push for discovering drugs to treat them.

With broader genetic knowledge, some mysteries are being unraveled, offering explanations and, in some cases, the promise of new treatments.

“We estimate that about 80 percent of rare disorders have a genetic cause,” said Marsha Lanes, a genetic counselor with the rare-disorders group. Finding those genetic links is crucial to advancing research, she said.

And “if there’s a reason, some kind of underlying explanation for why this has occurred, that’s very satisfying for people, even if it doesn’t necessarily mean there’s a drug,” Lanes said.

The Cohens and other parents worked through the AHC Foundation to secure a 2010 Pepsi Refresh grant to finish genetic sequencing in about 100 children with AHC. Results of the study appeared in the journal Nature Genetics this past summer.

Researchers at Duke University in Durham, N.C., and the University of Utah in Salt Lake City found a common mutation in at least 74 percent of the children.

Asher wasn’t one of the kids with the mutation. But the Cohens now know that the gene affected in most of the children regulates sodium and potassium, both of which have a role in how the body creates electrical impulses. That’s far closer to an explanation than they were a year ago.

“Even if he doesn’t have the mutation, it’s something related to it,” Mr. Cohen said.

Nobody knows how the genetic mutation leads to the symptoms of the disease, but its identification will spur more research, said AHC expert Dr. Kenneth Silver, a pediatric neurologist at the University of Chicago and Comer Children’s Hospital.

The Cohens hope the knowledge helps researchers understand whether this rare disease is in some ways like a more-common disease, one that has proven treatments.

“Nobody is going to develop a drug for 1,000 kids, but you can start asking what else is out there that impacts the sodium and potassium pumps,” Mr. Cohen said. “It opens up all these pathways. That’s the exciting part.”

And identification of a mutation is likely to lead to more diagnoses, to more parents who are getting answers and supporting one another, Mrs. Cohen said. “It’s a lonely place, to be Googling for answers. You feel very alone.”

Asher is doing well now. He’s in a preschool class that includes children with other developmental disorders and goes to physical therapy, occupational therapy and horseback-riding therapy.

The episodes of paralysis still happen about every two weeks, and some are painful and longer-lasting.

Still, his mother said, “Ninety percent of his life has been wonderful.”

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