By the time Jonathan Oliphint was 3 years old, his parents realized he had neurological and cognitive delays. He also had high blood pressure that doctors could not control.
Jonathan was born with a condition called argininsoccinic aciduria, or ASA, which meant his body could not break down certain toxins. ASA prevents the body from creating a critical amino acid that stops the buildup of ammonia in the body.
Too much ammonia can permanently injure the brain and other vital organs.
For 14 years, doctors and Jonathan's parents, who check their son's blood pressure every day at home, had struggled to figure out how to control Jonathan's swinging hypertension, while also holding the ammonia buildup in his body at bay. But clinical study of Jonathan over the years triggered new observations, and researchers hope the findings will help other people with ASA, which affects one in 70,000 newborns in the U.S., according to the National Institutes of Health.
"This is a beautiful story," said Dr. Brendan Lee, a professor of molecular and human genetics at Baylor College of Medicine who treated Jonathan. But the ending was long in coming.
"We'd check his blood pressure all the time and put him on a medication, but it would slowly inch its way up and we'd have to put him on another one," said his mother, Jamie Oliphint of Bridge City, Texas.
Lee gave Jonathan the supplemental amino acids to reduce the buildup of ammonia, but no matter the medication, Jonathan's blood pressure continued to rise.
Soon it was increasing at a rapid rate and not coming down.
"It seemed like, all of a sudden, it was just high," said Jamie Oliphint. "It wouldn't even be inching to higher levels anymore. It just stayed high, and no medication could bring it down."
Doctors also noticed that Jonathan's heart had become enlarged.
"We really had to look at what else could be happening in the body," said Lee.
Lee and colleagues realized that, because Jonathan's body could not make the critical enzyme that prevented the accumulation of ammonia, he also had a deficiency of nitric oxide, which was also linked to the missing enzyme. Along with many other functions, nitric oxide prevents heart disease by inhibiting clogging of the arteries.
So, Lee weaned Jonathan off the blood pressure medication and onto organic nitrate, a treatment often prescribed for patients at high risk for heart attacks.
"The bottom line is he responded terrifically," said Lee. "Within four days, his blood pressure normalized. What's been most amazing is that it's been almost two years he's been stable."
Jonathan's mother even said that her son's school test scores had improved since taking the medication, and he seemed more engaged with his peers and teachers.
By looking at the underlying layers of the disease and its causes, Lee said he and his colleagues hit on a treatment that they never would have found otherwise. Lee now has plans to study using organic nitrate in other patients like Jonathan who have ASA.
"This is only one patient whose results were quite dramatic, but there are so many other implications for disease," said Lee. "We haven't done a good job at targeting nitric oxide to treat disease. Our systems are so complicated that this could have broad implications for therapies for a variety of diseases.
"The patient's course led to observations that were then studied using technology that were then translated in a substantive way," said Lee. "It went from patient to bench to patient."