Timely Diagnosis – Genetic Services (Metabolic Diseases)
December 22, 2008
When Ty was born in January 2006, he was already engaged in a critical race against time. Even as his parents celebrated his arrival, even as he handily passed all initial health and newborn screenings, a tiny genetic mutation began to affect his development.
The stakes were high. If the disorder was quickly identified and treated, Ty could enjoy a normal life. If his particular “inborn error of metabolism” remained a mystery too long, his body would suffer permanent damage. He would become epileptic, mentally retarded, and unable to speak. His muscle tone would be forever weak.
An added challenge: At the time, Ty was probably one of only a few dozen children in the United States with the condition, and one of only several dozen identified world-wide. “It is hard to believe this is our story,” said Kim. “Especially since we know it might not have had a happy ending.”
Ty seemed completely normal, though he had trouble keeping food down, was thin and missed a few developmental milestones.
Everything changed one summer afternoon when Ty was six months old and the family attended a party. As Grant and Kim watched younger babies roll around, sit up, and play, they realized that something could be terribly wrong. Their little boy did none of those things.
The pediatrician validated their concerns and testing began. An MRI showed changes in the basal ganglia (the part of the brain that impacts movement and balance) that were consistent with a metabolic disorder. A urine organic acid test revealed that all the measured organic acids were elevated, but creatinine (a by-product of creatine phosphate in muscle) was low. However, since creatinine is often used simply as a reference point to evaluate the levels of other compounds, the doctors thought the creatinine level might be skewing the other results. Creatine itself is an essential compound that helps supply energy to muscle and nerve cells.
Unfortunately, there was no “aha” moment, beyond the indication that Ty might have a metabolic disease. The body’s metabolism converts food to energy; an abnormal chemical reaction that allows too much of one substance to be stored, or processes too little of another, disrupts the way the entire body functions. Because the process is complicated, it’s not easy to pinpoint problems.
As Ty began intensive physical and occupational therapy as part of the effort to reverse his particular muscular deficits, his parents contacted Rady Children’s Hospital-San Diego. Dr. Bruce A. Barshop, part of the hospital’s Biochemical Genetics and Metabolic Diseases program in the Genetics division, remembers meeting Ty. “His body was limp, simply unable to fight gravity,” Barshop said. “We find answers for the imponderable and his case was a challenge.”
More tests were run, but initially, the doctors remained stymied. Ty’s disease is rare, and fairly new (the first cases were reported in 1995). Additionally, his symptoms, including the poor growth, muscle weakness, developmental delays, and test results, mimicked certain fatal mitochondrial diseases. That was excruciating news.
“We could not believe that our child might not live past the age of 2,” said Kim. “We’ve never been lower than we were at that point.”
The doctors did not give up. “Mitochondrial diseases are diagnosed by excluding other options. Perseverance is needed to ensure we’re drawing the right conclusions from the data,” said Dr. Mary Willis, a biochemical geneticist at Rady Children’s. “Every patient deserves at least one doctor who goes to the mat for them, and doctors specializing in metabolics do that for a lot of kids.”
As the family prepared to visit Grant’s family in Arkansas for Thanksgiving, a blood creatine/guanidinoacetate test was run. “One test can diagnose any of three creatine disorders,” said Willis.
The doctors suggested that Ty be given a creatine supplement in advance of test results. The following week, Ty stood up in his mom’s lap for the first time. Grant and Kim had just returned home on November 30, 2006 when Willis called to say Ty had a creatine synthesis disorder named guanidinoacetate methyltransferase (GAMT) deficiency — and that it was treatable with a prescription liquid formula containing compensatory levels of creatine and L-ornithine along with a low protein diet. The disease occurred because both Kim and Grant carry one copy of the same recessive mutated gene; Ty had had a 25 percent chance of inheriting the condition.
When asked how long it took to pronounce the multi-syllable name, Kim begins to laugh. “No time at all,” she said: “I love those words – they gave my son his future. He finally had a diagnosis.”
Ty, who could not sit up on his own for his first birthday, now runs around his backyard and hit baseballs with his dad. He giggles easily and often, and skips around the house while deciding what to do next. Though he still receives speech therapy regularly, he’s graduated from the need for physical, occupational and visual therapies.
“Ty is strikingly normal,” said Barshop. “I expect he’ll catch up in all areas. It’s been gratifying to watch his progress.”
When he was 11 months old, with access to Rady Children’s Hospital resources and the dedication of his doctors, Ty and his family won the race against time that began with his birth.
Originally published in Kids’ NewsDay, San Diego Union-Tribune,
October 7, 2008.