Korean Twins With SMA Reveal the Cost of Missing Newborn Screening

Two babies, one missing test

A boy identified as B received gene replacement therapy for spinal muscular atrophy at 68 days old. His twin sister, C, received it at 76 days. Both children improved after treatment at Kyungpook National University Hospital, but their experience exposes a gap in South Korea: a medicine that works best before symptoms appear is available, while routine newborn screening for the disease is not.

Their mother, identified as A, had undergone extensive testing before their birth following a difficult journey through in vitro fertilization. Yet none of those tests detected spinal muscular atrophy, or SMA. When B was about a month old, his cry became weaker and his breathing seemed unusual. Visits to a local emergency room and a neurologist eventually brought the family to the university hospital.

Professor Lee Yun-jeong, a pediatrician at the hospital, diagnosed B with type 1 SMA, a severe form that usually appears before six months of age. Examining his sister then led to another diagnosis, even though the family thought she was healthy.

Korean researchers have already documented the genetic frequency of SMA, and patient groups and medical societies have formally called for screening. Belgium offers a practical example of how regional testing can grow into national coverage. Together, these developments show what Korea would need to connect its treatment system with diagnosis immediately after birth: targeted testing, laboratories capable of delivering results quickly and a direct route to specialist care.

Why a few weeks matter

SMA damages motor neurons, the nerve cells that carry instructions from the spinal cord to muscles. Without enough survival motor neuron protein, those cells deteriorate, weakening the muscles used for movement and breathing. Treatment aims to preserve their function before more damage occurs.

Type 1 accounts for about 60% of newly diagnosed SMA cases, according to Lee. Without treatment, most children with this form die before age two or need respiratory support. She cited an average interval of 3.6 months between the first symptoms and a definitive diagnosis.

Lee described the urgency she faces when a child with type 1 SMA reaches her clinic:

every day is an emergency.

Zolgensma, whose generic name is onasemnogene abeparvovec, delivers a working copy of SMN1, the gene that normally supplies instructions for making the protein. Earlier treatment gives doctors a better chance to protect motor function while more nerve cells remain.

Lee said damage can begin before a baby looks unwell. A newborn screening program would look for the genetic cause before families or doctors have to recognize weakness. That changes the starting point of care from responding to illness to identifying a baby who needs urgent assessment.

What the twins experienced

C reached testing through her brother's diagnosis, a process known as family cascade testing. Lee noticed that she lacked deep tendon reflexes, the automatic muscle responses doctors check during an examination. She requested testing through Pusan National University Hospital's rare disease diagnostic support program. The result came back four days later.

Lee described C as already being at a subclinical stage: disease changes were present even though obvious symptoms had not yet appeared. Within a week of diagnosis, her muscle tone had slightly decreased.

The family experience followed a short but consequential sequence:

• At about one month old, B developed a weaker cry and unusual breathing.
• After B's diagnosis, Lee examined C and requested genetic testing because of absent reflexes.
• Four days after the request, C's test confirmed SMA.
• B received Zolgensma at 68 days old, followed by C at 76 days.
• One month after treatment, B's motor function score had risen from 17 to 35.

Doctors assessed the children using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, or CHOP-INTEND. It measures movement and strength on a scale with a maximum of 64 points. B began at 17; C began at 28 and improved to 44 after treatment. Their gains were 18 and 16 points respectively, while C started treatment with more motor function.

For Lee, the sister's diagnosis illustrates why waiting for visible weakness can lose valuable time. C received attention because her brother was ill and an examination revealed a warning sign. Routine screening would create a route to testing for babies without an affected sibling.

What a targeted genetic test would look for

SMA screening typically looks for a missing section called exon 7 in SMN1. Exons are portions of a gene used to make protein instructions. A targeted test checks for a particular genetic change, so the presence of other genetic test results in a family's medical file does not mean that SMA has been examined.

The Korean SMA information service Together in SMA, operated by Biogen, states in its SMA diagnosis guidance that Korea's newborn screening does not include the condition. It describes molecular genetic testing of a blood sample to identify SMN1 changes and assess SMN2 copy number.

SMN2 is a closely related gene that produces a smaller amount of useful survival motor neuron protein. Having more copies can partly compensate for faulty SMN1, helping explain why severity varies between patients. Doctors use the result alongside a child's examination and other findings.

The guidance says SMN gene deletion test results generally take three to four weeks, depending on the institution. C received her result in four days through a diagnostic support program. For a national screening system, laboratory speed and access to an urgent specialist appointment would both matter.

Reduced muscle tone, sometimes described as floppiness, can be an early sign. Several genetic conditions can cause it, which makes prompt access to appropriate testing important when a baby shows weakness.

Korean research puts numbers behind screening

A study published in Annals of Laboratory Medicine examined 1,581 anonymous Korean newborn cord blood samples. Its Korean carrier frequency study identified 29 SMA carriers, or 1.83%, approximately one in 55 newborns. No sample had deletion of both SMN1 copies.

SMA is usually inherited in an autosomal recessive pattern. A carrier generally has one working SMN1 copy and one affected copy without having the disease. When both parents are carriers, each pregnancy generally has a one in four chance of a child inheriting an affected copy from each parent.

The researchers calculated an estimated incidence of SMA caused by SMN1 deletion of one in 11,815 births. Using Korea's 357,771 births in 2017, they estimated about 30 affected babies annually. Lee's current planning estimate is about 25 new SMA patients a year.

Applying the study's estimated incidence to the 250,000 newborns Lee proposes using for screening capacity planning gives roughly 21 babies with SMA caused by SMN1 deletion per year. The calculation is 250,000 divided by 11,815. It helps put the scale of testing and the expected number of affected children in the same frame.

The study also identified limits to its laboratory method, multiplex ligation-dependent probe amplification, or MLPA, which counts gene copies. It can miss certain small genetic changes and carriers with two SMN1 copies on one chromosome and none on the other. The authors said carrier frequency could therefore be underestimated. Planning a screening service would require a defined route for further investigation when symptoms or family history warrant it.

Diagnosis can take years in other forms of SMA

Researchers at Gangnam Severance Hospital examined a different part of the diagnostic problem: people with types II and III SMA, whose symptoms generally begin later than those of type 1. Their diagnostic journey study, published in Yonsei Medical Journal, reviewed 38 patients using records from January 2000 to September 2023.

The median delay between symptoms and diagnosis was 19.6 years. It was 21 years among the 29 patients with type III and three years among the nine with type II. The study came from a single neurology department focused largely on adult patients, including people with later or atypical symptoms.

About two thirds initially received another diagnosis. Type III patients were often thought to have muscular dystrophy, while developmental delay was a common initial diagnosis in type II. Before SMA confirmation, 92% underwent needle electromyography, which records electrical activity in muscles; 58% had a muscle biopsy; and 53% underwent genetic testing for muscular dystrophy.

All 38 ultimately had deletions in SMN1 exons 7 and 8. The authors described wider access to SMN1 testing and increased interest following the Korean introduction of nusinersen in 2019 as factors bringing more patients with unusual or later symptoms to diagnosis. Their findings add another task alongside newborn screening: improving recognition and targeted testing among people already living with unexplained weakness.

Belgium shows how regional screening can expand

Liesbeth De Waele, a pediatric neurologist at University Hospitals Leuven in Belgium, described a staged approach that resembles Lee's proposal for Korea. Southern Belgium introduced SMA newborn screening in 2019, and coverage expanded nationwide in December 2022.

De Waele said Belgium considered the World Health Organization's Wilson-Jungner screening criteria. These ask practical questions: whether a disease is serious, whether it can be detected, whether effective treatment and care are available, and whether the benefits justify the resources required. Belgium also examined public acceptance and the value of treatment before symptoms.

A comparison between southern and northern Belgium, presented at the World Muscle Society, found better motor outcomes among children treated before symptoms, according to De Waele. She also described benefits in quality of life and economic assessments. The regions' different starting dates allowed researchers to compare care within the same country as screening expanded.

Belgium still had to build laboratory capacity. De Waele identified genetic testing infrastructure and equipment as practical challenges. Many established newborn tests measure hormones, enzymes or other substances; SMA requires genetic analysis and the staff and equipment to perform it.

Her recommendation for Korea was to study earlier programs and organize what happens immediately after diagnosis. A positive screening result needs to trigger confirmation and treatment decisions without avoidable waiting.

A Korean policy proposal already exists

The Korea Rare Disease Association announced an SMA screening white paper on July 22, 2024, produced with the Korean Child Neurology Society and the Korean Newborn Screening Society. It recommended introducing newborn screening so an irreversible disease could be diagnosed and treated early.

Lee proposes pilot programs across regions and medical institutions to establish the resources needed for screening about 250,000 newborns annually. The work could also guide changes to laws and regulations. No national implementation date was given.

Daegu and North Gyeongsang Province are her proposed base for a regional SMA diagnosis, research and care network. Kyungpook National University Hospital already operates as a regional rare disease center and neuromuscular disease center.

Lee wants a referral system that sends babies identified through screening directly to specialists, supported by education for obstetricians, gynecologists and administrative staff. Families now often visit several local hospitals before reaching her team. A regional network would aim to replace that search with a clear sequence of testing, confirmation and care.

Treatment coverage also requires lasting support

Zolgensma became eligible for reimbursement in Korea in August 2022. Under its agreement linking payment arrangements to treatment outcomes, responses must be assessed and reported every six months for five years. Lee, who manages five patients treated with the medicine, said the work requires specialists, coordinators and administrative staff and places particular strain on hospitals outside the capital region.

Lee called for a national registry that would combine follow up across rare diseases and treatments:

"Rather than maintaining a separate long-term reporting system for each rare disease and each treatment, we need a national system with an integrated registry that automatically evaluates patients' clinical progress and treatment effects," she said.

Some children treated early, including patients with three SMN2 copies, can develop almost normally, Lee said. Outcomes also depend on disease severity, gene copy number and treatment timing. Some patients continue to need musculoskeletal care and other support as they grow.

The twins' improvement makes the benefits of treatment tangible. Their different starting scores also show why Lee wants diagnosis moved closer to birth. For families, an effective system would bring together screening, rapid confirmation, treatment access and continuing care, reducing the time spent searching for answers while a child's muscles weaken.

Key Points

• Korea does not routinely include SMA in newborn screening, although treatments are available.
• Twins B and C received Zolgensma at 68 and 76 days old and both gained motor function after treatment.
• A Korean study found 29 carriers among 1,581 newborn samples, approximately one in 55.
• A July 2024 white paper recommended SMA newborn screening; Lee proposes regional pilots and direct specialist referrals.
• Belgium expanded regional SMA screening to nationwide coverage in December 2022.
• Lee also seeks an integrated national registry to reduce the burden of tracking treatment outcomes.