Routine test reveals rare diseases

By Peter Jurich, Waisman Communications

It used to be called floppy baby syndrome and it looks just as it sounds. The technical term is hypotonia, and it’s when newborns lack the muscle strength to resist passive movement; their muscle tone is much like a ragdoll. While hypotonia is not a disorder in and of itself, this condition is a harbinger of other disorders — some of which researchers lack an understanding of because they are classified as “rare.” One of those rare diseases is spinal muscular atrophy, or SMA, a rare and devastating muscle-wasting disease that affects one in every 11,000 children in the U.S.

February 29 is Rare Disease Day, which aims to raise awareness of such rare diseases. And while specific treatments for most of them may be far on the horizon, learning to identify them can raise both public awareness and research funding. Today, one of the best ways to identify rare diseases is through newborn screening.

Mei Baker, MD
Mei Baker, MD

“The newborn screening is most likely the first test of your child’s life,” says Mei Baker, MD, co-director of the Newborn Screening Laboratory at the Wisconsin State Lab of Hygiene and a Waisman Center affiliate investigator. There are two point-of-care tests to screen for hearing loss and critical congenital heart diseases. Newborns also have a heel prick in which a drop of blood is collected 24 to 48 hours after birth and then sent to the Newborn Screening Laboratory at the Wisconsin State Laboratory of Hygiene where a screening panel is performed. The panel tests for 47 diseases, 46 of which are rare. A rare disease is defined as one that appears once in every 2,000 or fewer in the general population.

Newborn screening and Baker made headlines in Wisconsin in early February when a baby born in Wisconsin became the first to be successfully identified with SMA through newborn screening. This is significant, especially considering that the test for SMA was just added to the Wisconsin newborn screening panel in October 2019.

“A child with this genetic defect does not produce a very important protein that keeps motor neurons healthy, without which the neurons die,” says Baker. She describes the condition as “heartbreaking” because children with the most serious form of SMA need a respirator to assist their breathing, and they’re often bedridden. Without medical intervention, 80% of patients with the most serious form of SMA will die by the age of two years. There is hope and a treatment but only if the disorder is identified early on. Enter the importance of newborn screening. “Every day, every hour matters,” Baker says.

Continuing a mission

Newborn screening is the most successful public health undertaking since the 1960s, with a rich history particularly at the Waisman Center. The center’s founder, Harry Waisman, MD, PhD, was an early champion of screening newborns for phenylketonuria, or PKU, a rare metabolic disorder that, if untreated, could lead to intellectual and developmental disabilities. Thanks to his efforts, PKU is a mainstay on newborn screening panels throughout the U.S. and, thanks to that early identification, individuals with PKU can live healthier lives.

Today, Baker continues Harry Waisman’s legacy of advancing research and knowledge about rare diseases and newborn screening. “All populations get rare diseases, so that makes newborn screening beneficial to all,” Baker says. She underscores the importance of studying rare diseases even though they are not often on people’s radars. “It’s harder to draw attention to rare diseases,” she says. Rare diseases are sometimes disregarded in both research and the general public because, individually, they don’t have a high prevalence within the population. Competing for attention against better known diseases can often keep research and treatments of rarer ones hidden.

But, Baker says, by looking at them as a cumulative public health issue, maybe more attention and research funding can be drawn their way. “Rare diseases are important health issues because when you group all rare diseases together, the collective incidence is high enough to be an important public health problem.”

There is now, she says, a growing interest in neuromuscular disorders (NMDs) from a newborn screening perspective, and Baker focuses her research there. She recently led a pilot screening program for Pompe disease. Pompe is an inherited and rare NMD. Patients with Pompe also have muscle weakness like SMA. She hopes the pilot experience has a positive impact when considering adding Pompe to the Wisconsin newborn screening panel.

“We know the science is there,” she says, “but what does adding it to a routine screening program look like?”

Mei Baker lab
Baker reviewing and discussing a testing results with Sean Mochal and Michael Cogley.

Overcoming obstacles

Baker is first author on a paper that discusses newborn screening for NMDs. The paper, “Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy through Newborn Screening,” describes some of the legislative barriers researchers must overcome at both the state and federal level, and stresses the importance of early recognition and treatment of rare diseases. The paper proposed a blueprint for getting other NMDs — specifically Duchenne muscular dystrophy, or DMD — approved for screening panels.

According to the paper, “As new interventions for neuromuscular disorders become available, the clinical community must prepare to overcome the challenges of adding new diseases to screening panels and understand the rigorous evidence review at the federal level and the complex process of state-level implementation.”

One of those challenges is this: in order to be approved for screening, a rare disease must have an effective treatment available. But to develop that treatment, there must be research, for which, as Baker said above, it’s harder to find support and funding if the disease is rare. Though early detection can save lives, there are program challenges at multiple levels. “The more we study a disease, the more likely we are to find treatment,” Baker says.

While clinicians agree that early diagnosis can lead to additional therapeutic options for DMD, the lack of broad genetic-defect-targeted treatment prevents it from becoming part of the newborn screening panel. While the decision in the U.S. to add new diseases to newborn screenings is made at a state level, they are often first added at the federal level to the Recommended Uniform Screening Panel (RUSP). For diseases to be included on the RUSP, researchers must also prove that a disease represents a public health issue.

It can take years to add a new disease to the RUSP, but despite this sometimes long and challenging process, progress is still being made. For example, Pompe disease was added to RUSP in 2015, and SMA in 2018.

Investing in the future

According to news reports, the baby who was diagnosed with SMA is doing just fine today after receiving gene therapy treatment. This is all thanks to the funding and public support that made it possible to early identify this rare disease through a newborn screening test.

“I really want parents to understand that this is a public program for your child that focuses on your child’s health,” Baker says. “The diseases we’re screening for don’t have obvious symptoms until it’s too late.” Diseases on a newborn screening panel cannot be detected at birth by a general physical exam.

“Newborn screening is not just a test,” Baker continues. “It’s a program and a system. We need everyone working together – from the birthing hospital getting good samples, to the laboratory doing high quality testing, to the physician following up after screening.”

Baker says there is no feeling comparable to the work she does helping a newborn who needs it.

“Newborn screening saves lives. With newborn screening, I really think you can make a difference,” she says. With the structure and resources available to her on the UW-Madison campus, Baker has been able to work on improving the newborn screening process for better identification of rare diseases. “When you know the effort you put in and you see the result of healthy babies, nothing can compare with that,” she says. “I think I’m very lucky to be in this profession.”