Three-year-old Carmen Akras’ big brown eyes dart to her little brother, Albie, as he races around the sunny living room of their Hampden home.

Crash! Albie dumps a bag of Legos on the ground. Tap! Tap! Tap! Albie whacks the sofa legs with a toy hammer. Thonk! He drops a book.

The edges of Carmen’s mouth quirk into a smile. The rest of her body is still: delicate hands, graceful legs, small feet in cuffed lace socks.

It was not always like this. Eighteen months ago, it was Carmen zipping around this room, giggling, babbling and piling toys on top of her baby brother. When Albie bounced in his walker, Carmen would toddle over, turn on music and start a sibling dance party.

What their parents, Tom and Annie Akras, did not know was that a genetic disorder was already beginning to erode Carmen’s nerve cells. Soon, the couple would notice Carmen was becoming wobbly, struggling to eat and not talking as much as her peers.

In October 2024, Kennedy Krieger Institute doctors diagnosed Carmen with late infantile onset metachromatic leukodystrophy, or MLD, a recessive genetic condition that destroys the nervous system and affects one of every 40,000 babies in this country.

Most children with MLD as severe as Carmen’s do not live to their 5th birthday.

Annie left her teaching job so she wouldn’t miss a moment with her daughter. She made sure Carmen received every possible therapy to prolong her abilities, ease her discomfort and extend her quality of life.

Carmen’s family watches as she slowly disappears into herself. She spends her days snuggling her parents’ arms, resting on the sofa or reclining in the BabyBjörn lounge chair Albie used as a baby. A small pink and purple backpack holds the pump that pushes nutrition into her feeding tube.

Erin Bull, a nurse from the Gilchrist Kids pediatric hospice program, comes to the house every week to cuddle with Carmen and support the family. Lately, they have been broaching tough questions about the future.

“I watch Annie with Carmen and the way she touches her cheek and see how much she loves her,” Bull said. “But there is a piece of my heart that breaks when I watch her with Carmen because I know the impending loss.”

Compounding the Akrases’ grief is the knowledge that an effective test and new gene therapy exist for MLD. Carmen was diagnosed too late to receive the treatment.

That could soon change for other children.

Last year, the U.S. Food and Drug Administration approved a gene therapy called Lenmeldy that can stave off MLD symptoms when children are identified and treated in the first months of life.

Receiving the drug is a grueling process that requires infants to take strong chemotherapy and spend months in isolation. At more than $4 million, Lenmeldy has been called “the world’s most expensive drug.”

But its benefits are priceless; Lenmeldy can extend a child’s life.

Meanwhile, the test for MLD is simple and relatively inexpensive: a heel prick performed at birth or the first pediatrician visit, a red dot of blood sent to a lab. While babies born in Maryland each year are tested for a slew of genetic disorders, MLD is not among them.

New York is the only state to require newborn testing for MLD. Advocates in Maryland and several other states are pushing to include MLD in routine newborn screenings.

And the federal government appears poised to include MLD in the Recommended Uniform Screening Panel, which many states, including Maryland, abide by. The U.S. Department of Health and Human Services invited public comment on the proposal earlier this year.

Although Lenmeldy had not yet received FDA approval when Carmen was born, the Akrases could have gotten her into a clinical trial had she been diagnosed sooner. With an average of 65,000 babies born each year in Maryland, odds are at least one of them is destined to die in childhood from MLD without treatment.

“I want to educate people,” Tom said. “I don’t want people in Maryland to ever have to deal with this again.”

A genetic time bomb

When Annie Rochfort and Tom Akras married on the grounds of The Manor Tavern in the summer of 2021, a heavy rain streamed down the sides of the tent. It felt like a blessing, a shower of joy.

She was a former college lacrosse player and Fulbright scholar who had returned to Baltimore to teach Spanish at Notre Dame Preparatory School, her alma mater.

He was an attorney who was working for the Downtown Partnership of Baltimore after stints on the city liquor board and in the Baltimore state’s attorney’s office.

They had no way of knowing they both carried a gene that made a faulty version of a key enzyme. Any child they conceived would have a 25% chance of developing MLD.

In August 2022, Carmen arrived. “Introducing Baltimore’s newest hon,” read the birth announcement.

In the accompanying photo, baby Carmen raises her small fists, her eyes crinkled with delight. That was the theme of the first two years of Carmen’s life: pure joy.

Family photos show her crowing with laughter in her car seat. Beaming in a pink dress while pushing a doll stroller, a pink bow resting on her brown curls.

“She was a little bit sassy,” Annie recalled. Carmen’s hobbies as a toddler included trying on her mother’s shoes, playing princess and covering Albie — 14 months younger — with sticky hugs.

As Carmen approached her 2nd birthday in the summer of 2024, the Akrases began to notice she was a little late meeting milestones.

Her once voracious appetite gave way to eating challenges. She seemed increasingly unsteady on her feet, falling frequently.

The couple took Carmen to see her pediatrician, an eye doctor, an ear doctor, a neurologist. A physical therapist worked with her at home. Finally a Kennedy Krieger Institute clinician recommended an MRI.

Annie logged into a virtual meeting to learn the results of the testing. Tom, who had been appointed to the state alcohol, tobacco and cannabis board, was running late.

“My husband isn’t here yet, but everything is OK, right?” Annie remembered asking nervously.

The doctors would not answer. When Tom arrived, they broke the news gently.

A distinctive pattern of white stripes appeared on Carmen’s brain, a telltale sign of MLD. The disorder would systematically rob Carmen’s neurons of their protective covering, exposing them to damage like electrical wires stripped of their rubber coating.

It was not just that Carmen was late meeting milestones. Soon her development would plateau and then reverse.

Carmen’s future milestones would be losses. The last time she walked. The last time she crawled. The last time she sat up unassisted. The last word she spoke.

As the disease bored its way into her brain stem, she would lose the ability to breathe without assistance. Eventually, her heart would stop.

Tom, ever the attorney, cross-examined the doctors.

Did they have patients with Carmen’s condition who were 2? Yes.

Did they have patients who were 5? Yes.

How about 10?

The doctors paused, then shook their heads. No.

‘A perpetual hole in our family’

Shortly after Daniel Sullivan of Frederick was diagnosed with MLD in 2014, his family went on a Make-A-Wish trip to a toy robot factory.

Daniel, then 3, was beginning to lose control of his limbs, but he was still able to laugh with delight at the tumbling robots.

The pace of losses escalated after the trip.

“The thing about metachromatic leukodystrophy is because it progresses so rapidly, you’re constantly dealing with new symptoms,” said Daniel’s mom, Susan Sullivan. “Right after the diagnosis, seeing Daniel lose the ability to walk and lose the ability to talk. That was the worst.”

Like Carmen’s parents, Dan and Susan Sullivan found care for Daniel at Kennedy Krieger and Gilchrist Kids hospice before his death in 2018.

Seven years later, the family has kept his bedroom the same: stuffed Thomas the Tank Engine on his bed, robot stickers on the wall, a quilt made from his favorite T-shirts.

“It’s definitely a perpetual hole in our family,” Susan said. Daniel’s younger sister often speaks of how much she wishes he were around to look out for her.

Susan has channeled her grief into advocacy. She organized fundraisers for Gilchrist Kids and Make-A-Wish.

She sent so many emails to Maryland’s Advisory Council on Hereditary and Congenital Disorders that they invited her to become a citizen member of the board.

“Every year we don’t do this in Maryland, the odds are that another child is born whose life could be saved,” Susan said.

She has traveled to Capitol Hill to ask lawmakers to add the disorder to the diseases for which infants are screened at birth.

Earlier this month, she attended a congressional briefing and reception about MLD screening. The speakers included Carmen’s physician, Dr. Eric Mallack, the clinical research director at Kennedy Krieger’s Moser Center for Leukodystrophies.

The event was hosted by Orchard Therapeutics, the makers of Lenmeldy.

A miracle drug?

The quest to develop an MLD therapy began 17 years ago in Milan, Italy.

Researchers created a treatment in which a patient’s stem cells are extracted from their blood and the defective gene is replaced with a functional version. The stem cells are then reintroduced to the child’s bloodstream, where they travel throughout the body and begin replicating.

After clinical trials showed strong results, the European Union approved the treatment in 2020. It took another four years before the Lenmeldy therapy was approved for use in the U.S.

“The treatment has the ability to transform the lives of children,” said Benjamin Navon, a spokesperson for Orchard Therapeutics.

MLD can appear in adults and children of all ages, but it most commonly emerges in the late infantile period, between 6 months and 2 years. The disease also progresses most rapidly in these patients.

Since the disease is rare and is not routinely screened for at birth, most clinical trial participants were MLD patients’ younger siblings, who also carried the faulty genes.

Of the 37 children who took part in the study, all lived to celebrate their 6th birthday, Navon said. About three-quarters of them were able to walk without assistance, and all had an IQ and verbal skills within a normal range.

But the treatment is not easy.

The babies, and their caregivers, must travel to one of five treatment centers throughout the country that partner with Orchard, including the Children’s Hospital of Philadelphia. The baby is hooked up to a machine that filters stem cells out of the blood.

The stem cells are shipped to Milan, then the frozen, repaired stem cells arrive back in the U.S. four to six months later.

The child receives a powerful chemotherapy that kills off the stem cells in their blood and bone marrow, then they get an infusion of their repaired cells. The process temporarily depletes the child’s immune system, and they usually remain hospitalized for about three months as they regain strength.

Private insurance or Medicare has covered the $4.25 million treatment for every child who has qualified, Navon said. “There were no coverage denials,” he said.

For Susan, the fact that an effective treatment exists is a compelling reason to begin routinely screening all infants for MLD.

“Newborn screening is a public health issue,” Susan said. “The test needs to be accurate, affordable, and there is an effective treatment available. MLD is a slam dunk on all those fronts.”

Day by day

Annie bends close and nuzzles her daughter’s cheek. “Carmen, Carmen,” she breathes in a singsong voice in the girl’s ear. “It’s time for your medicine.”

Beside them on the floor is a bin filled with syringes of medications to shoot into Carmen’s feeding tube. One prevents seizures. Another helps unlock her tight limbs. A third dulls the pain of muscle spasms.

Suddenly Albie gallops across the floor and takes a flying leap onto his mother’s back as she leans over his sister. “Horsey! Horsey!” he yells, clinging to her shoulders. “Play horsey!”

Tom and Annie are often struck by the contrast between their children. As Albie, who does not have MLD, has grown ever more active and inquisitive, Carmen’s become progressively more still and silent.

The first few months after Carmen’s diagnosis were a blur of doctors’ appointments and therapy sessions — occupational therapy to help Carmen maintain some manual dexterity, physical therapy in a heated pool to help her seizing limbs, speech and swallowing therapies.

None of this stopped the march of white stripes across Carmen’s brain and the slow death of her neurons.

First she used pink braces to get around. Then a walker. Now Annie carries her everywhere.

“The Akras family has been dealt an unimaginable hand, but they have gone above and beyond to help Carmen,” said Mallack, the Kennedy Krieger physician.

By last winter, Carmen was struggling to eat and aspirating food. She would wake her parents in the night, calling “hiya, hiya, hiya,” a word she used to mean “hungry.”

After consulting with several doctors, Annie and Tom decided in February to have a feeding tube implanted into Carmen’s stomach. With it came challenges.

She could no longer walk after the procedure, and she had trouble keeping food in her stomach. Annie and Tom experimented with different formulas, delivery speeds and medications, but Carmen grew thinner and weaker.

By late spring, Carmen could not sit unassisted. Physical and occupational therapies, which had once seemed like playtime at Kennedy Krieger, were no longer enjoyable. Annie pulled her out and focused on the simple pleasures of summer — a trip to the beach, a walk to the playground, the feel of sunlight on her face.

In August, the Akrases enrolled Carmen in the Gilchrist Kids program. The hospice team found a feeding tube protocol that Carmen could tolerate: pureed chicken and vegetables delivered in a slow stream for 16 hours a day.

Carmen slowly began to gain weight again. Her Gilchrist clinicians adjusted her medications so she would remain alert but be free from pain. “It has really given Carmen a second wind,” Annie said.

A music therapist arrives each week to sing and strum the guitar. An art therapist works with both children.

The couple’s relatives and friends have circled around the little family. Annie’s sister, Grace Rochfort, lives a few minutes away and comes over frequently. Both sets of grandparents babysit often, enabling Annie to return doctors’ phone calls or blow off steam at the gym. Friends, including Annie’s Notre Dame Prep classmates, organized a fundraiser this fall to help defray medical costs.

As she cares for Carmen and Albie, Annie has undergone several rounds of IVF. The couple wants Albie to grow up with a sibling after Carmen is gone.

“I don’t even know if he’s going to be able to remember Carmen — that’s the crazy thing,” Tom said.

Annie, who has been at Carmen’s side almost constantly since the diagnosis, struggles to think about the inevitable parting.

“I don’t have a death wish,” she said. “But no mother would want to send their 3-year-old off somewhere by themselves with no way to check on them.”

This month, the family traveled to Orlando courtesy of Make-A-Wish, visiting SeaWorld and Disney World.

Carmen, who last year toddled around in a Snow White costume, met an actor dressed as the princess. Annie cradled Carmen in her arms, studying the girl’s face for subtle signs of joy.

“She just has this look when the wind blows across her face,” Annie said. “It’s like, ‘Yes, this is where I’m meant to be.’”