It started with a slight twitch. Steve and Gay Grossman both noticed it in their daughter Lilly in 1998, when she was just one-and-a-half years old. By the time she was four, the twitches had grown into full-blown muscle tremors. They wracked her whole body at night and were painful enough to wake her up.
The family stopped sleeping properly. Lilly would wake up, shaking and crying, as often as 20 or 30 times a night. During the worst bouts, Steve and Gay took shifts to console her, one staying with her until two in the morning and the other taking over from there. "I can't describe what it's like to care for a baby, a young child, who's crying and shaking all night," says Steve.
The Grossmans have dealt with this for the last 13 years and, if anything, Lilly's tremors became more frequent and more severe. They eventually started happening during the day. She developed muscle weakness, poor coordination and balance problems. She had to use a walker until middle-school and a motorised wheelchair thereafter. She was often very tired.
Then, in the summer of 2012, the tremors stopped. For 18 days, Lilly slept soundly through the night. So did Steve and Gay. "We had dreams again," he says. "We had forgotten what that was like."
This U-turn in Lilly's fortunes was the result of a study called IDIOM, led by the father-and-daughter team of Eric and Sarah Topol at the Scripps Translational Science Institute in La Jolla, California. IDIOM stands for Idiopathic Diseases of Man—that is, "serious, rare and perplexing health conditions that defy a diagnosis or are unresponsive to standard treatments". In other words, whatever Lilly had.
The Scripps team sequenced Lilly, Steve and Gay's complete genomes. Amidst the morass of As, Gs, Cs and Ts, they identified the likely causes of Lilly's mystery condition—three mutations in two different genes. One of these pointed the way to a potential treatment—a drug called Diamox that had helped another family with a fault in one of the same genes. When Lilly tried it, she gained a few weeks of sound tremor-free sleep.
"Whole-genome sequencing can change lives and maybe save some," says Steve. "It changed ours." It was no miracle—the tremors have returned to a lesser extent than before, and the team are pursuing new leads. But Steve and Gay never expected The Answer. They didn't anticipate an easy cure. Genomics gave them something arguably more important—hope. It turned the nameless, unknowable ailment that had stolen years of sleep from their daughter into something tangible—a condition with a cause that can eventually be addressed. And it bought them time with Lilly.
Two – Not Knowing
Lilly's life has been defined by both the condition that restricts her choices, and the smarts, tools and support that allow her to escape those restrictions. Gay recalls, "Ever since Lilly was really small, she'd be up most of the night and in the morning, I'd say, "Why don't you stay with me and relax?" And she would just cry and cry to go to school. She always wanted to be doing what the other kids were doing."
Schools can make many children feel isolated or different, but they have always been great equalisers for Lilly. Her weak muscles and sensitivity to warm temperatures meant that, at home, she missed out when other kids played outside. At school, everyone sat and so did she. She got to use a brain that, tiredness aside, has stayed untouched by her physical symptoms. "She's a regular teenager—smart, sarcastic, funny—and she has a grade point average of 3.5," says Steve.
Lilly became a technophile out of necessity. Since pens and books are painful to hold, she has used laptops since kindergarten. Her voice tires easily and she hates it when people talk to her like she's deaf or infirm; when she got her first cellphone and started sending texts, her social life blossomed. She was always good at maths but since drawing figures was taxing, she gravitated towards English and reading-heavy subjects. She now fancies herself a writer, penning pieces for her school newspaper, posts on her blog, and an online book about disability called Through My Eyes.
Through all of this, Steve and Gay have worked tirelessly to support her. She designs a stationery line called Letters from Lilly and spends her day "arguing with insurance companies and school bureaucracies". He works at a software company with links to aerospace and defence and sources all the technology that allows his daughter to live as independently as possible. When it came time to tell Lilly's story, Gay wrote three pages of text. Steve prepared a PowerPoint presentation.
For the longest time, the duo were bedevilled by uncertainty about Lilly's condition and the belief that her time was slowly running out. Doctors initially diagnosed Lilly with cerebral palsy, but that wasn't it. Next came a diagnosis of glutaric aciduria, leading to a modified diet and a lot of support groups. That wasn't it either. The next guess was the heartbreaker: some kind of mitochondrial disease. These disorders affect the tiny bean-shaped batteries that power our cells. They vary a lot, but given the harsh and relentless nature of Lilly's symptoms, Steve and Gay were worried. "The life expectancy for a teenager isn't so great," he recalls.
Printed out, Lilly's medical records take up two four-inch binders. She's had MRI scans, blood draws, spinal taps, skin biopsies, nerve biopsies, and a muscle biopsy. The tests hinted at a few depleted nutrients that could be fixed by supplements, but for the most part, they said the same thing: Lilly seemed normal. "We've been from world-class people to alternative quacks," says Steve. No one could offer them the surety of a true diagnosis, much less a suitable treatment.
"Every birthday was a hard one—missed milestones and another reminder that we still didn't know what's wrong with her," says Gay. When would the sand eventually run out? This year? The next one? "When you don't know what you're dealing with, and you're up all night with your kid crying and shaking like crazy, you think: Does anyone even remember this is going on? Nobody knew what to do with us."
More ...
http://phenomena.nationalgeographic.com/2013/03/11/we-gained-hope-the-story-of-lilly-grossmans-genome/?src=longreads
