LAB’S STANDARDS MISSED BABY’S SERIOUS DISORDER
UNIFORMITY LACKING IN STATES’ SCREENINGS
By the time he got to the emergency room, Leo’s lips were blue, his chest heaved up and down. The 16-month-old struggled to breathe.
Based on the level of acid in his blood, doctors were sure the Minneapolis toddler had swallowed something he shouldn’t have: Nail polish remover? Aspirin? Antifreeze? His dad rushed home to check the cabinets, the car, below the sink, everywhere, trying to figure out what the little boy might have gotten into.
But Leo Carleton-McMahon hadn’t gotten into anything. Acid had been building in his blood since he was born in 2014, the result of a rare, yet treatable metabolic disorder.
Like nearly all newborns, Leo had his heel pricked shortly after birth to screen for genetic disorders affecting about 1 in 800 babies. His results were normal — at least that’s what a report from the Minnesota State Lab said.
It was a year and a half later — the end of 2015 — when Leo’s parents learned a marker on his newborn screening had actually been just below the cutoff used in Minnesota to flag his genetic condition.
It was too late. It was after Leo had a stroke. After he suffered brain damage. After the little boy could no longer walk.
Doctors determined Leo has methylmalonic acidemia, a disorder where his body can’t break down certain proteins and fats. With a regulated diet, a child with the disorder can develop normally — that’s the point of newborn screening. But Leo hadn’t been treated, so acid built up in his blood, causing the stroke and damage to his brain.
Because of what happened to Leo, the company contracted to do newborn screening in Minnesota’s state lab lowered the cutoff for a marker that could have caught his disorder. In January of 2016, the cutoff was dropped from 0.40 to 0.37 — meaning a baby with levels at 0.37 or higher would be flagged. Leo had been at 0.38.
Babies like him will now get a closer look — but only in the few states that happened to make the same change. And only because Leo’s mom pushed to find out why her child’s condition had been overlooked.
This haphazard approach is common in newborn screening, where each state runs its own program and sets its own standards to detect serious genetic disorders.
Policies and protocols vary widely between states, some of which don’t follow scientific standards or even common sense, the Milwaukee Journal Sentinel found in an investigation.
As a result, a child who suffers brain damage in one state might be diagnosed and treated in another. A baby’s chance of having a deadly condition detected — averting death or brain damage — can be based on arbitrary decisions, cost-cutting and politics.
Five months before Leo was born in 2014, the State of Minnesota signed a contract to have a private laboratory handle much of its newborn screening. By going with PerkinElmer Genetics instead of the Mayo Clinic, the state would save about $10 per sample.
For the previous decade, the Mayo Clinic had done some of the state’s screening for $22 per sample. After losing the contract, a researcher at the Mayo Clinic terminated the state lab’s access to software used to improve the accuracy of newborn screening. Mayo developed the free software under a federal grant and controls access to it.
On a recent evening, Stephanie Carleton sat on the floor in her living room, reading to her son. Now 21⁄ 2, Leo can’t stand by himself and has a hard time speaking. He’s fed formula through a tube in his stomach.
When Leo was still in the hospital after his stroke, Carleton wanted to know how her son had been missed. She asked doctors for his newborn screening results — all she could see was a list of “Nega
tives,” not actual test numbers.
She contacted the state lab. Staff there started to investigate, checking with PerkinElmer and neighboring states to compare cutoffs. Though its cutoffs were similar to those used by other states, and more conservative than some, PerkinElmer lowered the number used to flag abnormal results, Minnesota health department officials said.
“Did it make me happy? No,” Leo’s mom said. “It didn’t matter for him. We helped everyone else’s kid, but not our own.”
The Journal Sentinel found that state labs often don’t change cutoffs or policies until after a child dies or suffers irreversible harm, even when aware of problems with testing procedures, such as not considering a baby’s age when blood was collected — a factor that can significantly affect results.
There is no authority or federal policy to ensure that improvements made in one state are adopted in another. ‘OUR FIRST KID’ Leo was the first baby for Stephanie Carleton and Josh McMahon. The baby had a hard time breastfeeding at first but soon began gaining weight. At six months, the pediatrician noticed he had low muscle tone.
When Leo wasn’t walking at 12 months, his pediatrician said she’d do an amino acid test at his next appointment if he was still behind. Leo’s dad took him back three months later but said the doctor never did the test, which would likely have found high acid levels in the baby’s blood.
A month later, Leo was up at 2 a.m., vomiting.
The next morning the same thing happened. A doctor prescribed a steroid and anti-nausea medicine, but Leo got sicker throughout the day. His limbs were floppy. He couldn’t stand. That’s when he started breathing hard, and his lips began to turn blue.
At the hospital, Leo was put on a ventilator. It took two days for doctors to determine he had methylmalonic acidemia, or MMA.
Once he woke up, Leo had lost words he once knew. He couldn’t control his arms; they flailed about.
His mom, pregnant with his little sister, grew terrified the same thing would happen to her next baby. And she wanted to know why this had to happen to Leo, especially since newborn screening was supposed to catch MMA.
The small spot of blood collected from a newborn’s heel is used to generate results for dozens of metabolites that help detect as many as 58 disorders, although some states test for as few as 31. Biology expresses itself differently in each person, and many factors influence the metabolites analyzed to detect disorders. Labs use various equipment and methods to do their tests.
The software developed at the Mayo Clinic was designed to take many of these factors into account. The software, known as R4S, draws on screening results from 30 million babies throughout the world, 19,000 of whom were diagnosed with metabolic disorders.
Instead of relying on cutoff values that may be arbitrary or outdated, labs can compare each newborn’s results with babies who have actually been diagnosed.
Piero Rinaldo is lead developer of the software and a clinical biochemical geneticist at Mayo Clinic. Rinaldo said personnel at the state lab had access to the webbased system since it was launched in 2008, but he decided to revoke it after the state didn’t renew the newborn screening contract with his lab at the end of 2013.
When asked why he blocked the state from using the software, Rinaldo said in a statement that the software and other advanced testing techniques developed to better detect conditions like MMA were fundamental components of the testing his lab had provided to the state for almost 10 years.
By choosing “another out-ofstate provider, one unwilling to participate in the collaborative effort and also not keen to use our software in their practice” it was evident that the Minnesota Department of Health didn’t want to continue with the same type of approach to screening, he said.
Dave Orren, chief legal counsel at the Minnesota Department of Health, said cost was only one factor in evaluating whether to end the contract with the Mayo Clinic. Mayo and PerkinElmer were assessed on the basis of cost and technical factors. Four of five reviewers ranked PerkinElmer higher on technical factors, he said.
When Leo’s results are put into the Mayo R4S database today, it warns there’s a possibility the baby has a disorder, and additional tests should be considered. It’s possible the software would have flagged him to be examined and diagnosed by a specialist for treatment when he was born, but it’s not certain because the software is continually updated as more cases are diagnosed.
Currently, the software shows about 25% of labs have a cutoff set even higher than the one used by Minnesota and PerkinElmer.
Leo’s mom said she often wonders why her son suffered a lifealtering stroke when newborn screening was supposed to protect him. She wishes the state lab and his doctors had been more aware of how close his test results were to the state’s abnormal cutoff.
“Everything about this makes me sad,” she said.