A 5-year-old's terminal MLD diagnosis gives her baby brother a chance to fight the rare disease

Anna and Joey Somers are inseparable.

When Joey was born, his 3-year-old big sister constantly wanted to hold and kiss him. Two years later, they scream with delight as they chase each other in the park or outside their Long Beach home, even if Anna sometimes stumbles and limps to keep up with Joey’s sprints.

"They’re very close," their mother, Millie Grennan, said. "Anna is absolutely obsessed with Joey. She loves him more than anything."

Anna also may end up saving Joey’s life — although she’ll probably never know it, and she may not live to see him grow up.

Last summer, Anna’s parents noticed the smart social butterfly who’d constantly make her parents laugh was becoming less focused. She’d stare off into space and wander around aimlessly. She'd sometimes not make sense when she talked.

"It was like the lights were on and nobody was home," her father, Joe Somers, said.

They also noticed Anna was tripping and falling a lot, sometimes returning from the playground with cuts and scrapes.

"We would say, ‘Anna is so clumsy, she would trip over her own shadow,’ " Somers said. "Now we understand why."

In December, Anna was diagnosed with a rare neurological disease, metachromatic leukodystrophy, which one of her doctors described as a childhood form of dementia.

That led physicians to test Joey and to find out that he, too, has the genetic condition.

Caught early enough, metachromatic leukodystrophy, or MLD, can be treated with a gene therapy that was approved in the United States in early 2024, just after Joey was born. At $4.25 million, it’s the most expensive treatment in the world. Doctors believe it may save Joey’s life.

But it’s too late for Anna.

The treatment only works if the child has no symptoms or very early symptoms.

MLD already has robbed Anna, now 5, of her ability to talk. Within months, doctors say, she may no longer be able to walk and will be put on feeding tubes.

The disease, untreated, is ultimately fatal. Children diagnosed at Anna's age live on average 10 to 20 years after symptoms first appear, with severe disabilities throughout most of their lives.

Joey, 2, doesn’t have symptoms, but if they surface and progress far enough, they could potentially render the treatment moot.

Since Joey’s mid-January diagnosis,  Grennan, 39, and Somers, 40, have gone through a whirlwind of hospital visits, mountains of paperwork and a panicked battle with Grennan’s insurance company in a desperate rush to start the treatment before it’s too late to save their son.

Millions of Joey’s stem cells are now in an Italian laboratory, where they’re being genetically modified. Next month, they’ll be infused into his veins. Then will come months of waiting to see how his body responds — and find out whether the procedure began in time.

You can’t be happy, because you’re saving your baby, but you’re losing your baby, too.

—Millie Grennan, mother to Anna and Joey

As the couple watch Joey undergo a potentially life-saving treatment, and simultaneously see Anna’s continuing deterioration, they try to work through their conflicting emotions. 

"You can’t be happy," Grennan said, "because you’re saving your baby, but you’re losing your baby, too."

It was only because of Anna's irreversible cognitive and physical decline that doctors thought to test Joey for MLD.

"It’s like sacrificing herself to save her little brother," Grennan said, her voice trembling.

Transforming treatment

Until recently, helping children and adults with rare diseases often has been limited to alleviating symptoms. Gene therapy is transforming how many of these illnesses are treated. In some cases, it stops them from progressing. It offers the potential of a cure for some diseases, or at least a significantly longer life, with or without disabilities.

But the cases of Anna and Joey illustrate that even with the huge advances in combating diseases like MLD, there are still children who face the same devastating prognoses as decades ago. And for kids eligible to receive gene therapies, there often are a lot of unknowns — and no guarantees.

Anna is one of many children with rare diseases diagnosed too late for gene therapy to help them.

When Somers, who works in billing for a commercial insurance company, and Grennan, who worked part time in an orthodontist's office but now takes care of the children full time, began worrying last fall that Anna’s clumsiness and the indecipherable things she was saying were more than idiosyncrasies, they took her to doctors for evaluations. Tests in November ruled out seizures. Just before Christmas, an MRI at Cohen Children’s Medical Center in New Hyde Park found nerve damage.

She was hospitalized as doctors tried to figure out the cause.

Children should progress developmentally as they get older, not go backward, said Dr. Jessica Gold, a Northwell Health geneticist and assistant professor of pediatrics at Zucker School of Medicine at Hofstra/Northwell. Anna went from speaking in paragraphs to talking in one- and two-word fragments.

"Whenever I hear about a kid who has developmental regression, I get worried that there's a genetic component to that," she said.

Northwell ordered genetic testing.

Anna tested positive for MLD. She had inherited the defective genes from her parents, who — as is usually the case with rare diseases — didn’t know they were carriers.

An estimated 1 in 40,000 to 1 in 100,000 U.S. babies each year — or about 35 to 90 — are born with MLD.

Children with MLD have a deficiency or absence of the ARSA protein, which helps protect the outer protective coating of nerves. Without it, nerves get damaged, causing cognitive and physical problems.

The new treatment for MLD, Lenmeldy, adds to stem cells a normally functioning gene that instructs the body to create ARSA. If successful, the treatment prevents the deterioration of the nervous system.

In clinical trials, Lenmeldy performed "beyond our wildest expectation," said Dr. Laura Adang, a neurologist at Children’s Hospital of Philadelphia who is helping treat Joey and Anna and is an expert in leukodystrophy.

The European Union approved the treatment in 2020, and the U.S. Food and Drug Administration followed in March 2024.

Lenmeldy is too new to determine if it provides lifetime benefits. Scientists will need to monitor recipients of the treatment for decades to know if it does. But researchers following children for an average of seven years after treatment found dramatically higher survival rates and far lower levels of cognitive and physical disabilities compared with kids who didn't receive Lenmeldy.

Gold believed that Anna’s symptoms were too severe to qualify for Lenmeldy. An IQ test at Children’s Hospital of Philadelphia confirmed that.

"Because the symptoms are non-specific at first, it can be almost impossible to find children in time," Adang said.

Because the symptoms are non-specific at first, it can be almost impossible to find children in time.

—Dr. Laura Adang, neurologist at Children’s Hospital of Philadelphia

It is typically only when one child begins declining that siblings without symptoms are tested, she said.

"Unfortunately, the story of Anna and Joe is one that we have seen over and over again," Adang said.

There’s now another way to detect MLD early: Newborn screening. New York in September became the first state to add MLD to its list of more than 50 rare diseases routinely tested in babies, although it’s only a one-year, federally funded pilot program that will expire in September if additional money is not found, said state Health Department spokeswoman Danielle De Souza. In December, MLD was added to the list of federally recommended newborn screenings, and more states are now testing.

If a baby tests positive, doctors can begin Lenmeldy treatment when it’s most likely to be effective, Adang said.

"We are in a race to save each child," she said.

Denied coverage

Once Joey was diagnosed, doctors began performing the tests and filling out the paperwork needed for insurance approval. His parents could never afford the treatment without it.

On March 4, Grennan received an insurance company letter familiar to many Long Islanders: "Denial Notice."

"The service is not medically necessary," the letter from Molina Healthcare, Grennan’s insurance company through Medicaid, stated.

Grennan was stunned. She knew that each day of a denial increased the risk to Joey’s life.

With its denial, Molina enclosed an appeal form that asks policyholders to state why they believe the company's decision was wrong.

"If he doesn’t get this treatment, he will DIE," Grennan wrote.

Dr. Mariko Bennett, a neurologist at Children’s Hospital who is helping treat Joey, wrote her own March 10 appeal, laying out how Joey met the medical qualifications for Lenmeldy, with a plea to the insurer, typed in bold: "Joseph is at the optimal time for treatment. Further delay by the insurance plan would cause unnecessary harm to the patient."

Molina finally approved the treatment in mid-April.

Molina declined to comment on its approval procedure for Joey. In a written statement, the company said: "Molina Healthcare’s priority is to ensure members receive medically necessary care consistent with evidence based clinical guidelines."

With very rare conditions like MLD, Molina must "carefully review all medical records and ensure that all appropriate arrangements are in place for any required treatments and procedures," the statement continued.

The small number of children with diseases like MLD is one reason gene therapies like Lenmeldy are priced so high, because there are few people who will purchase them, said Stacie Dusetzina, a professor of health policy at Vanderbilt University in Nashville, Tennessee, and an expert on the pricing of treatments and medicines.

The world's most expensive treatments are all gene therapies for rare diseases, and when London-based Orchard Therapeutics priced Lenmeldy at $4.25 million, there already were several others carrying prices above $3 million, according to pharmaceutical and technology publications.

Research into treatments is expensive, and many attempts at developing a medication or treatment end in failure, so prices also reflect unsuccessful research, Dusetzina said.

But in the United States, which lacks the price controls of Europe and elsewhere, "a lot of it is based on ‘what does a company believe it can get for a therapy,’ " she said.

Joy from every word

For children like Anna who are ineligible for Lenmeldy, "MLD is relentlessly progressive," taking away their basic functions to swallow, sit, roll and "even control their own head," Adang said.

Until that happens to Anna, her parents have tried to give their daughter as normal a social life as possible. After keeping her out of school for flu season, for fear of infection — her weak immune system means she is at risk of severe illness — they put her back into kindergarten in April.

"She’s so happy and excited to go," Grennan said. "All her teachers, everyone, they all say she is so happy all the time, always so happy, like endlessly happy. I guess that's a saving grace."

But Anna sometimes cries unexpectedly because, doctors believe, she may be frustrated that she can’t communicate as she used to.

So Somers always looks for ways to get his daughter to say something. When she can talk, even for a second, it brings joy to both of them.

One of Somers’ favorite ways to elicit a word from Anna is singing Christina Aguilera’s 2000 hit "Come on Over Baby (All I Want is You)" to her.

"I sing, ‘Come on over, come on over,’" he said.

"And she’ll always say, ‘Baby,’" he said, choking back sobs.

Somers knows Anna soon may be unable to even say that.

"It’s just happening so fast," Somers said. "One day she's going to wake up, she's not going to be able to walk, or they said she could wake up and she could be blind. So just preparing for the worst. But every day that she's not like that is good."

Hope

As Grennan and Somers steel themselves for Anna’s inevitable decline, they also are imbued with hope as they await the next phase of Joey’s treatment.

The couple last month took Joey to Children’s Hospital of Philadelphia — one of only eight hospitals nationwide authorized to administer Lenmeldy — for the stem-cell extraction.

Early in the morning of the first of three days that Joey spent there, Somers held his son down in their nearby hotel room to inject a drug that helps move stem cells out of the bone marrow and into the bloodstream so they can be taken out of his body.

Afterward, Joey clutched his beloved tan stuffed teddy bear as he walked toward the hotel elevator.

"That's Teddy," Somers said. "We don't go anywhere without it."

Teddy and Grennan stayed with Joey during the three days and two nights he spent in the hospital.

The tens of millions of stem cells extracted from Joey were then flown to the lab in Milan. Scientists there are using a harmless virus to spread a lab-created, working version of the gene that is defective in Joey through his stem cells. This gene will, research shows, instruct Joey’s body to make enough of the ARSA protein to protect his nervous system.

If all goes as expected, Joey will be admitted to Children’s Hospital in a few weeks to undergo chemotherapy to eradicate many of the defective stem cells to make room for the genetically altered ones. Then the modified stem cells will be infused into Joey’s body intravenously. He will spend between one and three months in the hospital, with doctors closely monitoring him.

Even after receiving Lenmeldy, some children have difficulty walking without assistance. That is a possibility for Joey, although as long as he remains without symptoms while the treatment gradually takes effect, Adang, the Children’s Hospital neurologist, said, the hope is he will be able to walk normally.

She said she’s optimistic, because siblings typically develop symptoms at roughly the same time, and Anna’s weren’t visible until she was 4. Joey turned 2 in February.

But there’s no way to know for sure if Joey will follow Anna’s path and not develop symptoms at his young age, Adang said. It can take six to nine months from when Joey receives the infusion next month for his body "to make ARSA in the right place," Adang said.

"That's part of one of the big challenges — that we aren't just looking at where the child is in the moment, we are looking at where they're going to be in six to nine months from then," she said.

The uncertainty weighs on Grennan and Somers. Will the treatment be too late? Will he live a normal life? Will he live, but with a disability?

Somers believes the treatment will work. But he knows it’s not a sure thing, and that while they’re waiting for it to begin providing protection, there’s a chance Joey could begin the same deterioration they’ve been witnessing with Anna.

"The scary thing about it is you know that the disease is in his body and it could take effect at any time," he said.

It would be hard to imagine Joey bedridden for the rest of his life, the couple said.

The scary thing about it is you know that the disease is in his body and it could take effect at any time.

—Joe Somers, father to Anna and Joey

"He thinks he’s the Hulk or Spider-Man," Grennan said. "He’s really a boy’s boy. He likes to jump around, wreak havoc, destroy."

"Do karate," Somers said.

"Yeah, lots of karate first thing in the morning," Grennan said.

In July, Grennan and Somers will move to Philadelphia for a few months to be with Joey while he’s in the hospital, and for a few weeks afterward, when he will need regular checkups.

Family and friends will stay with Anna and Robert, 11, Grennan's son from a previous relationship. The plan is to bring Anna to Philadelphia on weekends, but the couple agonize  over leaving her at home in Long Beach during what could be among her final months of mobility. The hospital advised that the couple should be Joey’s only visitors, because his immune system will be so weak to allow the treatment to work, and an infection could lead to serious complications.

After weeks or months away from home, the Anna  whom Joey will see when he returns to Long Beach may be a totally different person. She could be incapacitated, unable to run and play with the brother she has coddled and watched over since his birth.

It will be difficult for Joey to witness, Grennan said.

"While we were away at the hospital with Joey for his stem-cell retrieval," she said, "the only person he kept asking for was for Anna."