Genomic Data Helps Family Understand Son’s Mysterious Symptoms

by Tim Bonfield

 

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Advancing genomic knowledge is an integral part of our mission. The Center for Pediatric Genomics offers a variety of seminars for health professionals. Cincinnati Children's also integrates genomics into several fellowship, degree and professional certification programs. Learn more.

It took a revolution in medical science to provide the answers the Brunner family had been seeking for nearly 13 years.

When Tyler was born in 1999, it seemed like an early surgery to correct a birth defect involving his stomach would largely resolve his medical troubles. However, by age 2, Tyler developed seizures that seemed like an emerging case of epilepsy. By age 6, he was exhibiting bladder and bowel dysfunctions that suggested an autoimmune disease. As Tyler grew, he struggled to gain weight, became exhausted by normal activity and highly intolerant to heat. Strength faded from his legs to the point that he began using a wheelchair for relief.

“Not knowing what was going on was awful,” says Tyler’s mother, LaTonya Brunner. “He was sleeping on the couch constantly. His hands and feet would suddenly turn bright red and nobody could explain it.”

By 2013, however, increased speed and reduced costs had made whole-mitochondrial genome testing significantly more accessible as a diagnostic tool. In addition, Cincinnati Children’s had recently recruited an expert who knew exactly what to look for. It turns out that Tyler has a rare mitochondrial disease.

Taosheng Huang, MD, PhD, explains to Tyler Brunner and his mother, LaTonya, how the teen’s unusual symptoms might be caused by a rare mitochodrial disease.

Solving mysteries: Taosheng Huang, MD, PhD, explains to Tyler Brunner and his mother, LaTonya, how the teen’s unusual symptoms might be caused by a rare mitochondrial disease, which occurs in approximately one in every 5,000 births

IMPROVING DIAGNOSIS

Taosheng Huang, MD, PhD, a geneticist from the University of California Irvine, arrived in fall 2012 to direct the new Mitochondrial Disease Program at Cincinnati Children’s. Known as the “powerhouses” of cells, mitochondria produce over 90 percent of the energy required by a cell. However, when dysfunctions occur, a wide variety of neurological and organ system complications can result. The new program, based in the Division of Human Genetics, integrates genetic testing, translational research, and clinical care for these children.

Tyler’s condition occurs once in every 5,000 births, scientists estimate. If there was ever a set of conditions that needed the power of high-throughput genomic analysis and the promise of personalized medicine, this is it.

“This is the time for improving diagnosis,” Huang says. “With more precision, we have a better chance of finding more effective treatments.”

Tyler has already benefitted from better genetic testing. He takes a vitamin cocktail known to help improve energy levels for some children with “mito.” Over time, researchers hope to find treatments that can more directly address specific forms of mitochondrial disease.

The Huang lab has identified many new mito disease-causing genes. For example, in July 2015, Huang’s team published findings in Nature Genetics based on whole exome analysis of four families from different countries who share an identical set of gene mutations that have caused an unusual combination of optic atrophy and peripheral neuropathy affecting their vision and their legs, respectively. The team managed to produce a zebrafish model, and has recently begun work to produce a mouse model to resolve how these genetic abnormalities lead to the patient’s symptoms.

PATHWAY TO TREATMENT

Eventually this work could lead to a new drug compound, or possibly a stem cell transplant approach, that could improve mitochondrial function across a wide range of variations. “This would be a remarkable advancement for both science and the patients suffering from mitochondrial diseases,” Huang says.

LaTonya Brunner says she hopes that Tyler may personally benefit from a breakthrough treatment, but even if that does not happen, participating in the research work has been valuable.

“A couple of years ago, we didn’t know anything about mito. It’s a very hard disease to explain to other people,” she says. “Now the word is starting to get out.”