Correct diagnosis has toddler walking

DURHAM, N.C. — The last thing Wes and Melissa Klor want to do is rein in their son when he darts around like 18-month-old toddlers are apt to do.

Just six months ago, the couple had no hope their baby would ever walk, much less run.

As an infant, John Klor failed to reach normal physical milestones and was diagnosed with cerebral palsy.

But last summer, John was discovered to have a rare metabolic disorder that affected his ability to process protein, creating a toxic assault on muscle and brain function.

A fairly simple dietary change, along with supplements, resulted in a swift turnaround. Within days and weeks, John went from being unable to bear weight to crawling, pulling up and walking.

"It was really unbelievable," said Wes Klor, 28.

Now doctors and scientists at Duke University Medical Center, where John is being treated, are laying the groundwork for a study to determine whether John's metabolic condition — GAMT deficiency — should be included in the battery of disorders North Carolina screens for in its routine infant blood tests.

John Klor had a rough arrival May 28, 2008. His umbilical cord wrapped around his neck, causing a shortage of oxygen to his brain. He initially didn't score well on newborn assessments, but after 24 hours on oxygen, he was fine.

Problems surface

For a few months, he tracked along with his peers, but then he fell behind and even regressed. He rolled over a few times but stopped. He laughed and cooed, then quit. He had increasingly poor control of his head. He constantly swirled his hands in a fluid wave.

At his six-month checkup, his pediatrician confirmed the Klors' fears that John wasn't developing normally and referred them to a neurologist. There, John was diagnosed with cerebral palsy, a broad term describing varying levels of impaired movement.

A major factor in the diagnosis was John's delivery, because oxygen deprivation often leads to brain damage.

The Klors were devastated.

"We left that office not knowing what to do," Melissa Klor said. The neurologist was so sure of the diagnosis that she didn't insist they get a brain scan for confirmation.

Melissa, 27, said she was prepared to fill her days at their home with regimens to help John. Wes, a former Marine who continues to work on Harrier jets as a private contractor, re-evaluated the dreams he had for his firstborn son.

"We were ready to have to spend a lot of time taking care of him," Wes Klor said.

But the Klors decided to seek a second opinion from a neurodevelopmental specialist, Dr. Karen Harum.

Harum told them John had some classic symptoms of cerebral palsy, including the repetitive hand motions, but she wasn't convinced. She urged the Klors to get additional blood tests and the brain imaging to rule out other causes.

The brain scan, an MRI, showed little of the telltale damage to the parts of the brain that characterize cerebral palsy. And John's serum tests, which had been sent to Duke to be read by genetic experts, were unusual.

A urine sample revealed a surprising result — a condition so rare the genetic group figured the screener had run the test incorrectly. They ran a second test and it came back identical.

Protein culprit

John had a genetic disorder in which he wasn't processing protein properly.

The biochemical genetics lab at Duke, using tandem mass-spectrometry technology and a biological procedure that Duke scientists developed, is one of two in the country that can test for the type of disorder afflicting John.

The Duke team discovered John's condition was GAMT deficiency (guanidinoacetate methyltransferase) . About 40 cases have been described in the medical literature worldwide since the deficiency was identified in 1994.

The GAMT gene tells the body how to process protein into energy for muscles and the brain.

A faulty gene can cause a major disruption in that synthesis. It's as if a dam occurs in the protein stream, so certain nutritional building blocks clog to toxic levels on one side, while other essential components aren't released on the other side.

The result is damage to the body and brain that increases over time, including developmental delays, lack of speech, seizures, movement disorder, mental retardation and autism.

John Klor's treatment started immediately after the diagnosis in late June. For the rest of his life, he can eat very little protein, and instead must take a supplement that gives his body the amino acids it needs.

"We do suspect these disorders are underdiagnosed," said Jennifer Goldstein, a genetic researcher at Duke who was involved in the diagnosis.

Because no one tests for them, they aren't found, so they may actually be less rare than the literature would suggest. And that may mean some children who could be helped are, instead, diagnosed and treated for other profound disabilities — to no avail.

The Duke team hopes it can collect the data to make a case for including GAMT in the state's infant-screening program, which catches an average 230 metabolic and genetic disorders each year.

The tests, using five drops of blood collected on every baby born in hospitals, began in the 1960s to catch cases of PKU, a treatable malfunction in the processing of amino acids. North Carolina was among the first in the nation to begin screenings for dozens of disorders in 1997, using mass spectrometry and a process developed at Duke.