Nixing the Newborn Screening Advisory Committee Is Ill-Advised

Next month, families affected by the rare genetic disease metachromatic leukodystrophy (MLD) will meet in Washington. They will be protesting the April 4 dissolution of the committee of experts that advises Health and Human Services (HHS) leadership on which conditions to include on the Recommended Uniform Screening Panel, aka the RUSP.

The List
RUSP is a state-by-state roster of up to 61 “actionable” metabolic conditions. If they are detected shortly after birth with a few drops of blood from the heel, treatment is possible. But it must begin ASAP.

The RUSP is not part of FDA. Instead, it is “a list of disorders that the Secretary of the Department of Health and Human Services (HHS) recommends for states to screen as part of their state universal newborn screening (NBS) programs.”

The Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) suggests to the HHS Secretary conditions to target. The committee is vital, because the politically-appointed Secretary need not have an advanced degree in a health or scientific field, but a “deep understanding” of health and human services. A Secretary whose expertise is in law – perfectly legit – would likely not be familiar with such conditions as isobutyrylglycinuria, spinal muscular atrophy, or medium-chain ketoacyl-CoA thiolase deficiency.

Killing the advisory committee is especially frustrating for parent groups trying to get their illnesses added to the list. It can take years. MLD and Duchenne muscular dystrophy were slated to join the RUSP next month – neither is on the most recent update from July 2024. Adding these two conditions, experts say, would identify 400 to 450 babies a year whose lives could be saved, with gene therapy.

But the family groups won’t back down. The webpage banner for Parent Project Muscular Dystrophy reads: “The Future of Newborn Screening for Duchenne: Moving Forward After the ACHDNC’s Dissolution.”

Calliope’s Diagnostic Odyssey

Newborn screening detects metabolites in blood that indicate a specific disorder. This is life-saving if no one in the family has the condition to indicate elevated risk, and especially if symptoms do not arise or are recognized for months or years, but a treatment only works if started ASAP. That’s the case for some gene therapies.

When diagnosis comes too late to treat the condition, it is heartbreaking.

That was the case for a little girl named Calliope Joy, who had MLD. Her mother, Maria Kefalas, is a professor of sociology at Saint Joseph’s University in Philadelphia. She was integral in pursuing the gene therapy for other families, even though Calliope Joy couldn’t benefit from it. Kefalas tells her story in her compelling book Harnessing Grief: A Mother’s Quest for Meaning and Miracles. (See The Calliope Joy Foundation)

The disbanding of the advisory committee pulled the rug out from under Kefalas.

“It has been horrible, but I am hopeful we are getting people interested in the story. We are bringing the gene therapy families to DC on the day the vote was supposed to happen,” to include MLD on the testing panel, Kefalas said in an email.

Because Calliope Joy didn’t have an older sibling with the disease, her initial symptoms were confusing. First was an odd whole-body shuddering. After learning a few words, language acquisition stopped. Then her unbounded energy created issues in preschool. “It is accurate to say Cal ruined every class,” Maria wrote.

Developmental delays accrued, therapists descended, tests began. When their pediatrician saw the child walking on her tiptoes and unable to manage stairs, the next step was Children’s Hospital of Philadelphia.

There, MRI revealed the distinctive white matter brain changes of MLD. Then genetic testing confirmed the diagnosis – MLD is one of several types of leukodystrophy, which refers to the white matter of the brain. But it was too late for Calliope to benefit from the gene therapy.

Newborn Screening is One of the Greatest Advances of Modern Medicine

If I was asked to name the top ten medical advances of the past century, newborn screening would certainly be among them.

The technology may be complex, but the concept is simple: use knowledge of the body’s biochemistry to identify telltale signs in drops of a newborn’s blood that foretell development of a condition that can be treated, if action is taken early.

Activist families raise funds to have their affected relatives’ conditions added to the RUSP. The list varies by state (see Baby’s First Test). For example, West Virginia tests for 42 conditions, and California, 66. Baby’s First Test categorizes the entries: amino acid, endocrine, fatty acid oxidation, and hemoglobin disorders; lysosomal storage diseases; organic acid conditions; and others. It is jargony enough to reawaken nightmares of taking organic chemistry.

Years ago, an article in People compared two families whose babies had the same disorder – one child was treated and the other died, based on where they lived. For example, only a dozen states screen for Krabbe Disease, which is similar to MLD. Will ditching the advisory committee stop other states from adding Krabbe to their lists?

Newborn screening has been a staple of pediatrics for many years. I’ve covered it in all 14 editions of my human genetics textbook. And my graduate student in bioethics wrote a compelling history of the first newborn screen for an “inborn error of metabolism,” phenylketonuria (PKU). That first blood test identified newborns who could follow a strict “medical food” diet that prevents the disease’s brain damage. The Guthrie test for PKU is famous in the history of medicine, dating to 1961.

The value of newborn screening transcends the youngest among us. Findings can explain sets of symptoms and illnesses in other family members, which DNA Science recently covered in A Genetic Crystal Ball: When Newborn Genome Sequencing Findings Explain Illnesses in Relatives. Genome sequencing is more extensive than the heel drop screening, but heelstick findings for conditions that are very variable might explain health problems in relatives.

A Cut That Will Cost Young Lives

The announcement of ending the advisory committee of experts sent shockwaves through the rare disease community. Pamela Gavin, Chief Executive Officer of the National Organization for Rare Disorders (NORD), responded right away to the devastating news:

“Each year, newborn screening helps identify approximately 14,000 babies with serious conditions. Elimination of the ACHDNC risks the preventable death and suffering of children with treatable rare disorders. It is particularly crushing for the individuals and families impacted by conditions currently going through the RUSP nomination process who are left in limbo by this decision.”

CODA

When I read about the demise of the advisory committee, I immediately thought of seven children honored in the final sentence of the 2016 paper in The Lancet that reported the clinical trial results for the gene therapy for MLD, Calliope’s disease:

“In memory of Baily, Valentina, Carlos, Dennis, Liviana, Mustafa, Randa, and Amany.”

The suffering of those children enabled Alessandra Biffi and her team at the San Raffaele Telethon Institute for Gene Therapy in Milan to develop the gene therapy that is now saving lives – but only if children are identified soon after birth, before symptoms begin. It was the older siblings’ illness that signaled a younger sibling’s risk. With gene therapy, intervention is soon enough to counter the unfolding of the disease.

I cannot fathom the undoing of the Advisory Committee on Heritable Disorders in Newborns and Children, the brains behind newborn screening for preventable diseases. But nothing makes sense anymore in the anti-science dystopia that is now the US.