Leigh Syndrome/EARS2: Davis’ Story

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Davis at the park When Davis’ family first learned he had a rare and potentially life-threatening mitochondrial disease, Leigh syndrome, they took it day by day. “We prayed that we’d have more time with him,” remembers his mother, Tifanie. “Give us one year, two years.”

Davis is now 3, and the treatment he’s receiving at the Mitochondrial Medicine Frontier Program’s clinical center at Children’s Hospital of Philadelphia has his family planning for his bright future.

Difficulties from Day 1

Tifanie knew immediately that something was off with Davis, her third child, because he didn’t have the strength to suckle when she breastfed him. She would feed him with a syringe, managing to get a few tablespoons past his lips. Despite her diligent efforts, he wasn’t gaining weight.

Then at 3 months old, he regressed and became unable to hold up his head. Children’s Hospital of Atlanta, the closest pediatric hospital, suspected a mitochondrial disease and, when Davis was 5 months old, the family received a diagnosis of Leigh syndrome, a progressive brain disorder that is usually fatal.

After genetic testing, Davis was found to have a form of Leigh syndrome caused by inherited pathogenic mutations in the EARS2 gene. This specific mutation means that he is unable to make the proteins necessary for proper mitochondrial function.

In mitochondrial diseases, the mitochondria — tiny but powerful “batteries” that power each cell in the body — don’t function properly to make the energy that cells need to do their job.

The doctors in Atlanta told the family they didn’t have the expertise to treat Davis. “As soon as I found out, I made an appointment at CHOP,” Tifanie says. “It’s super scary, overwhelming really, when there’s not one doctor in your state who can treat your child.”

From Skeptic to Believer

Even though Tifanie brought Davis to CHOP’s Mitochondrial Medicine Program because of its reputation and expertise, she wasn’t ready to follow along unquestioningly with the individualized treatment plan Executive Director Marni Falk, MD, and Clinical Director Amy Goldstein, MD, created for him.

“There are so many knowledgeable doctors and support services at CHOP,” says Tifanie. “But I’m a skeptic. I came with a lot of questions. I questioned everything.”

She asked for research articles on EARS2-based mitochondrial disease, and they sent her a big stack. “I know all my thoughts and questions can be irritating, but they are patient and kind,” she says.

Because Davis was severely underweight at his first appointment in Philadelphia, the medical team proposed a feeding tube so he could catch up sooner. “I didn’t want a feeding tube at first, so we came up with an alternative feeding plan that worked,” Tifanie says.

She was also nervous about putting Davis on all the elements — supplements, vitamins and antioxidants — that were part of his recommended mitochondrial medicine “cocktail” all at once, “so we created a slower schedule where I could introduce one at time,” she says. “We disagreed but were able to come up with a plan that worked. I so appreciate their willingness to listen to me and work with me.”

From Struggling to Thriving

Davis baking cookies In the 2½ years since Davis’ first visit to the Mitochondrial Medicine Program, his health has improved tremendously.

He has gained enough weight that he’s now in the 20th percentile for his age. The stomach problems he had experienced earlier diminished once he was switched to a plant-based formula.

Like most children with Leigh syndrome, he initially had very low muscle tone. “He would just lie there,” Tifanie says. “Even smiling was hard because his little cheeks looked so heavy. He could not hold up his head or sit up.” Without intervention, he would have continued to decline to the point where he couldn’t swallow and would lose the ability to breath on his own.

And now? “Today, his physical abilities are the same as other kids’,” she gleefully reports. “He runs around, plays with his siblings. You would never know how weak he used to be.”

He also benefits from aggressive physical, occupational and speech therapy. “His main delay now is speech, but he still communicates very well,” Tifanie says. “He takes me by the hand and point to what he wants. He has a few signs, too, and that helps.”

The Secret Sauce

The turnaround in Davis’ health is largely attributable to his improved nutrition, including his mitochondrial medicine regimen. Twice a day he downs a small bottle that contains specific proportions of antioxidants such N-acetylcysteine (NAC) and ubiquinOL, vitamins like E, lipoic acid and biotin, and other supplements like folinic acid that provides folic acid for the brain.

In combination, these medicines are used to help manage his mitochondrial disease by targeting specific cellular deficiencies and providing proper cellular nutrition as a way to boost both his resiliency to stressors and his residual mitochondrial functions. Before starting the supplements, the function of his mitochondrial respiratory chain function was substantially impaired, which meant his cells lacked the essential process for making sufficient energy to power his cells and support a range of other critical metabolic processes in the cell.

What is especially tricky about treating mitochondrial disease with nutritional supplements can be that manufacturers of many of the ingredients do not need to follow strict government guidelines or standardized formulas that are required for FDA-approved pharmaceuticals. CHOP helps families mitigate that barrier by identifying trusted compounding pharmacies that source reliable supplements and create the mitochondrial medicine regiments according to the doctors’ specific instructions.

The Mitochondrial team connected Tiffanie to two pharmacies in Pennsylvania that compound Davis’s cocktail, work to obtain insurance coverage and ship it to them in dose-size bottles. “That is a huge help,” Tifanie says.

What’s Next

Davis with Tifanie Drs. Falk and Goldstein are so impressed with Davis’ improvement, he now comes to the Mitochondrial Medicine Program only once a year for a check-up and surveillance to identify any potentially new problems early. He has periodic tests to monitor the levels of an array of compounds in his body that mitochondrial disease patients may lack. He does not take any antiseizure medication, but does take oral arginine, an amino acid to provide a source of nitric oxide that may prevent metabolic stroke in Leigh syndrome patients.

He will eventually need an MRI of his brain to look for stroke-like damage in high-energy demand areas, but — since he cannot have anesthesia — that will wait until he’s old enough to lie still during the imaging. CHOP Neuroradiology has also worked with the Mitochondrial Medicine team to set up a rapid MRI without anesthesia that’s now available and can be effective to screen for metabolic stroke in Leigh syndrome patients.

Children with Leigh syndrome often have trouble fighting infections, but Davis has managed to hold his own and recently fought off a fever without having to be admitted to the hospital.

“Davis is a fighter,” Tifanie says. “He loves to play with his brothers and sister; he wants to be in the middle of everything. When we cook, he wants to help cook. When dad is working in the yard, he wants to work in the yard. When I clean, he cleans. He even has his own little vacuum cleaner. He loves being a good helper.”

There are only a about a dozen known cases of EARS2, and Davis’ transformation on the new formula and his mitochondrial medicine therapies has put him in a whole new sphere. “It’s been such a drastic change — for the better — I’m just trying to follow his lead. What can Davis do?” Tifanie says.

The family still takes things day by day, only now it’s with anticipation for what Davis will accomplish next.

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