In the days after his 5-year-old daughter died from a rare brain disease, Gan-Erdene Ganbat’s desperate focus turned to his younger child, Nomin.
Just 3 years old, she was already showing symptoms similar to her big sister’s. She was losing her speech, falling too often, walking slower than her peers.
It was an unimaginable terror, foreseeing the same fate for a second child, and it sent Ganbat and his wife, Davaasuren Zunzendorj, into a frantic search for the only treatment that promised any hope. In their native Mongolia, there was no way to get the drug: an experimental therapy available only in clinical trial. They were determined not to run out of time as they had with their older daughter.
After more than a year of searching and fighting, Nomin started taking the drug in November at UCSF Benioff Children’s Hospital Oakland. The hospital is one of only five sites in the world studying the treatment that Ganbat believes will save his daughter’s life.
“My hope is the medicine will work very well on my child — that if it doesn’t take it away completely it will at least stop (progression of the disease). Even that would be enough,” said Ganbat, speaking through an interpreter at the hospital this month.
He watched worriedly as Nomin, now 4, ambled around the sunlit lobby of the outpatient clinic, climbing low walls and grabbing for books and magazines to study. Her gait was unsteady, her limbs clumsy from disease, but she was obviously eager to explore.
“This is her last chance,” Ganbat said. “We know there is no other possible treatment for her.”
Extremely rare disorder
Nomin and her sister, Nandin, were diagnosed with a genetic disorder that falls under an umbrella of conditions called neurodegeneration with brain iron accumulation, or NBIA. The conditions as a whole are thought to occur in only 1 to 3 people per million, although they can be difficult to diagnose so the numbers may be higher.
The conditions typically hit children and are always progressive, although not necessarily fatal. No cure exists, and the only treatments target symptoms, not the cause of illness. The diseases primarily affect muscle function, from limb control to the ability to speak, chew and, eventually in some cases, the ability to breathe.
Cognitively, the children tend to be normal and suffer little if any mental degeneration.
The most striking biological sign of the disorders is the buildup of iron in a specific part of the brain called the basal ganglia.
“Most of the brain is normal. It’s really one tiny part that is kind of the control tower for integrating movements that becomes disabled with this disease,” said Dr. Susan Hayflick, a pediatrician and neurologist at Oregon Health and Science University in Portland who is one of the leading NBIA researchers in the world.
Hayflick said scientists don’t know how much the iron buildup actually contributes to symptoms. The iron, she said, may be more of a marker of disease — a side effect of some other biological malfunction.
Aiming at iron buildup
But the iron accumulation certainly causes some damage, both to the specific area where it collects and surrounding tissue that can be injured by iron oxidation, said Dr. Elliott Vichinsky, the director of hematology and oncology at Children’s Hospital Oakland who is leading the trial that includes Nomin.
The treatment he’s studying is aimed at preventing iron accumulation with a type of drug called a chelator, which is used to reduce toxic iron buildup in other diseases.
Vichinsky has treated a handful of other patients with the drug, and a few have shown signs of dramatic recovery. They aren’t cured, but he’s seen patients walk and talk again after being forced to use a wheelchair and unable to speak. About 30 children are enrolled in the current trial and will be followed for 18 months each.
“The (Ganbat) family, they wanted to do something to help (Nomin) after living through the nightmare of their first kid,” Vichinsky said. “My job is to make her better than she is now. And I can tell you, I’ve seen a lot of kids get better.”
Working toward a cure
Hayflick isn’t convinced that the chelator is entirely responsible for the improvements seen in some children. But she’s thrilled to see clinical trials under way and hopeful that as her group and others discover more about the cause and nature of the NBIA disorders, more treatments, and even a cure, will be available in the next decade or two.
Ganbat, though, has to hope that the chelator will be good enough.
It took more than a year to diagnose Nandin. Ganbat and his wife were told repeatedly by doctors that their oldest would catch up with other children her age. But she didn’t, and by the time she was 4, the delays were obvious and troubling.
They took Nandin to one of the top neurologists in Mongolia, who looked up the girl’s symptoms online and found a reference to NBIA. She translated the English page to Ganbat, but that was the best she could do. She told them to search online themselves for international experts in the disease and clinical trials that would give them access to experimental therapies.
But before the parents could make much progress, Nandin’s condition deteriorated. She turned 5 in June 2013 and was hospitalized a month later. She died this August, just before her sister turned 3.
Though they already had a diagnosis for Nomin and even a hint at possible drug therapy, Ganbat and his wife struggled to get her to treatment. They spent months trying to hunt down locations and contact information for clinical trials that might accept their daughter. Eventually a Mongolian woman who lived in the United States read about their situation on Facebook and agreed to act as a go-between for the family and researchers in Oakland.
Even then, the family faced repeated setbacks. The worst of them came at the very end, when their visa applications to travel to the United States were rejected twice. Finally, the U.S. Embassy agreed to grant visas only to Nomin and one parent; her mother stayed behind. The hospital is working with the embassy to try to get her mother into the country too.
“In our culture, we say if a child stays away from a parent, it’s like a disease. We’re afraid the sadness will lead to more disease,” Ganbat said. So Nomin and her mother don’t talk, and Ganbat erased most photos of his wife from his phone and an iPad. “They were making (Nomin) cry too much. It reminds her and she just starts crying.”
Home away from home
Ganbat and his daughter arrived in Oakland on Oct. 27. Since then, they’ve been living in a one-bedroom apartment with five Mongolian men in downtown Oakland. It’s all Ganbat and his wife, who run a small shop selling imported goods in the Mongolian capital, can afford.
He can’t work because his daughter requires around-the-clock supervision. She takes the trial drug twice a day — it’s too soon to say whether it’s helping her — and goes to the hospital once a week for blood tests to check for possible side effects. If not for the weekly blood draws, she could return to Mongolia for the course of the trial, but Ganbat said the lab tests aren’t available there.
Their days are spent entirely together, usually in the apartment, where Nomin draws or they play games. If the weather’s nice, there’s a park nearby to visit, and Nomin looks forward to their regular trips to buy groceries.
Ganbat has gotten used to being the primary caretaker, something that fell to his wife at home. On a recent visit to the hospital, Nomin’s hair was in a dozen tiny ponytails her father had tied all around her head.
It’s hard being here, so far from his life and his family, and knowing they must stay for at least another year and a half, Ganbat said.
“But we will make it here,” he said. “There is no other choice.”
Erin Allday is a San Francisco Chronicle staff writer. E-mail: firstname.lastname@example.org
Neurodegeneration with brain iron accumulation (NBIA) is a group of rare, genetic disorders that affect mostly children and cause a wide range of neurological issues, although symptoms mostly involve muscles.
Diagnosis: The disorders are marked by a buildup of iron in a specific area of the brain, the basal ganglia, that controls movement. The buildup can be detected on an MRI, which is one way the disorders can be diagnosed.
Symptoms: Symptoms include muscle weakness or stiffness; cramping or jerky, uncontrolled movements; tremors; poor balance; loss of speech; and loss of muscle control in the jaw and mouth, including the ability to chew. The disorders can be fatal.
Treatments: There is no cure or standard treatment. Some therapies are used to treat specific symptoms.
Experiments: Several sites around the world, including UCSF Benioff Children’s Hospital Oakland, are testing an experimental drug that removes iron buildup in the brain.
Donations to help Nomin and her family with housing and other needs can be sent through the Children’s Hospital and Research Center Foundation. Go to http://bitly.com/1rfXmad and direct the donation to “other,” then type in “NBIA fund.”