Greyson’s diagnostic odyssey began just five days after he was born when his pediatrician sent him to the Cook Children’s Emergency Department.

“We were admitted into the NICU, where Greyson spent the next six weeks,” said Sarah Pathipphanith, Greyson’s mother. “There we discovered he had a host of problems including low muscle tone, apnea and dysphagia. We met many of our current doctors during that stay.”

Every rare disease has unique characteristics, but they sometimes share similar symptoms. This is where genetic testing comes in handy.

“PURA Syndrome can be characterized as a neurodevelopmental condition where individuals who are affected typically have global developmental delays, intellectual disabilities and difficulties with expressive language,” said Candace Gamble, M.D., medical director of the Cook Children’s Genetics Center. “The hard part in the beginning is that these symptoms are present with many other genetic conditions, so we used a type of genetic testing called whole exome sequencing to identify genetic variations and rule out other diagnoses to discover the super rare.”

Once the genetics team uncovered Greyson’s diagnosis, they guided his family through the results and connected them with other families in the community who have children with similar diagnoses. Now, he regularly sees a variety of Cook Children’s specialists: genetics, neurology, pulmonology, orthopedics and the Child Study Center.

“We felt very relieved to have answers and a framework for Greyson’s future treatments,” Pathipphanith said.

Despite his diagnosis, Greyson knows happiness and humor. His mother says he lights up every room with his sweet smile, big eyes and contagious chuckle.

“He loves to clap and play instruments when listening to music,” Pathipphanith said. “He likes to go on walks with his gait trainer and is very determined to explore his world!”

Dr. Gamble says Greyson will write the story of what PURA syndrome means for him.

“We’ll adjust to his needs,” Dr. Gamble said. “What makes us unique at Cook Children’s is that we serve as an advocate as we follow each patient along their health care journey. We can’t cure their genetic condition, but we work to make their lives better.”

This week, SMA was added to the list of required medical screenings every baby in Texas receives at birth. Without newborn screening, many children escape the diagnosis until after permanent neuromuscular damage has occurred. Early recognition and treatment can mean the difference between a near normal life or suffering many skeletal deformities and being unable to breathe without a ventilator.

“The hope and thought is that it’s going to change the lives of patients and their families,” said Stephanie Acord, M.D., a pediatric neurologist at Cook Children’s Jane and John Justin Neurosciences Center. “Without treatment, these kids and those who care for them are significantly affected. The earlier you treat SMA, the better.”

Dr. Acord directs the multi-disciplinary Muscular Dystrophy Association (MDA) Clinic at Cook Children’s Jane and John Justin Neurosciences Center where she and Warren Marks, M.D., medical director of movement disorders at the center, specialize in the treatment of SMA. Dr. Acord shared with us what every expectant parent needs to know about the disorder and the new screening.

What is SMA?

Spinal muscular atrophy is a genetic disorder in which the nerves within the brainstem and spinal cord, called alpha motor neurons, break down and lose the ability to send signals from the brain to the muscles. Without those signals, the muscles grow weak from lack of use and affect a baby’s ability to hold up and control their head, sit up, crawl, walk, swallow, speak and breathe. If left untreated, a child will eventually require a feeding tube and respiratory support, such as a ventilator. Untreated SMA is among the leading genetic causes of death of infants and children.

Spinal muscular atrophy can be passed to a child if both parents have a defective survival motor neuron (SMN1) gene. Parents do not have the disease or signs of the disease and do not usually know they carry an abnormal gene. The faulty gene inhibits the production of the protein that fuels these motor neurons and, without it, the nerves die. There is a back-up copy, the SMN2 gene, but it doesn’t work as well as the SMN1 gene.

It is estimated that about 100 children born in Texas each year have the disorder. Many newborns will not show signs of SMA for months. By that point, you’ve lost valuable treatment time and the ability to give a child with SMA a better life. This is why newborn screening is so important.

What are the signs and symptoms of SMA?

There are several types of SMA. Symptoms vary depending on the type, but muscle weakness and loss of muscle control that worsens over time are general indicators. It is important to note that SMA is not a cognitive disorder, but a muscular one.

Type 0 is the rarest and most severe form of the disorder. Babies born with Type 0 SMA have breathing problems very early on and typically do not survive.

Type 1 is the most common form of SMA and also considered severe. Infants will begin showing signs within six months of life. They have poor head control, do not sit independently and have difficulty sucking and swallowing. Even though cognitively they are normal, they are unable to speak due to weakness. Without treatment they will need assistance with breathing, feeding, communicating, sitting and walking.

Type 2 is a more moderate form of the disorder. Symptoms will become evident between six months to 18 months of life. Infants with Type 2 will have difficulty controlling their lower limbs. They may be able to sit independently and crawl but struggle with walking.

Type 3 is a milder form of SMA. Symptoms such as mild muscle weakness, difficulty walking or frequent respiratory illness do not appear until after 18 months of life. Some people may not experience symptoms until early adulthood.

Type 4 is adult onset SMA. It is rare, progresses slowly and typically doesn’t appear until the early 30s. Most people maintain mobility and are able to manage their symptoms without much interruption to their lives.

What treatment is available for SMA?

The Federal Drug Administration (FDA) approved the first treatment for SMA in December 2016.

“It used to be a diagnosis in which there was very little treatment and little hope,” Dr. Acord said. “But the treatment now available for these patients is completely different than it was just five years ago.”

Today, there are three FDA-approved treatments. Two—Spinraza® and Evrysdi®—are drug therapies that help stimulate the production of a more functional SMN2 protein. These two treatments require ongoing administration of medication at various time intervals. The other—Zolgensma®—is a gene-replacement therapy administered once through an IV that delivers a normal functioning copy of the SMN1 gene.

The treatments have varying degrees of success, but all work to improve the strength and function of muscles through healthier neurons. They help to prolong the amount of time a child can live without additional support such as equipment to help them breathe more comfortably, as well as increase their ability to speak with their voice and to eat to some extent by mouth. The most critical part of any of the treatments is to start as soon as possible following diagnosis.

How will my newborn be screened for SMA?

As of June 1, 2021, SMA is one of 55 disorders on Texas’ list of required newborn screenings. It does not require an additional test. It’s simply bundled into the routine screenings already performed on newborns via blood test.

What happens if my newborn is positive for SMA?

If your newborn’s screening is positive for SMA, it is recommended that they be referred to a specialist, either a pediatric neurologist or a pediatric neurogeneticist, within 24 hours. A specialist will most likely conduct additional testing to confirm the diagnosis and develop a treatment plan.

“Parents need to advocate getting their child to a specialist as quickly as possible,” Dr. Acord said about receiving a positive SMA screen.

Pediatric neurologists at Cook Children’s Medical Center are able to conduct many SMA assessments virtually via telemedicine, which is helping parents and children in parts of the state without specialists get access to care from the comfort of their home.

Click here to learn more about the Muscular Dystrophy Association Clinic at Cook Children’s and for contact information for clinic staff.

Charlee was diagnosed in utero with congenital hyperinsulinism (CHI)—a rare genetic disease of the pancreas. Although there are several forms of the disorder, hyperinsulinism is a condition in which the pancreas produces too much insulin, driving blood sugar levels dangerously low and depriving the brain of important fuels it needs to function.

"Hyperinsulinism is a rare condition affecting about 1 in 20,000 to 30,000 newborn babies each year," said Paul Thornton, M.D., medical director of the Cook Children's Hyperinsulinism Center. "However, it is the most common cause of severe hypoglycemia in the newborn. Despite this, unfortunately today, there are still patients who have delays in diagnosis. This can be very damaging as this form of hypoglycemia puts babies at a high risk of brain damage."

The Perkins are no strangers to the disorder as their 11-year-old daughter, Ava, was also born with CHI. Even so, the pandemic made the somewhat familiar situation much more challenging.

Babies born with CHI need a quick and correct diagnosis and immediate intervention with medication to increase blood sugar levels. Without these measures, they can suffer seizures, brain damage or even death for a disease that can be managed with various therapies and, in some cases, even cured with surgery. An amniocentesis revealed Charlee’s CHI prior to his birth, giving the family important information they needed to prepare for his arrival.

The first major hurdle was to determine where to deliver Charlee. He would need care at a medical facility with a center specializing in CHI. Only two of those exist in the U.S.—one at the Children’s Hospital of Philadelphia (CHOP) and the other at Cook Children’s Medical Center in Fort Worth. The Perkins were familiar with the center in Philadelphia as that is where Ava received treatment shortly after her birth, but the pandemic made traveling that far from home complicated. They needed something closer, preferably a facility a reasonable car ride away.

An internet search led the Perkins to Cook Children’s where they were put in touch with Dr. Thornton who trained at CHOP and is considered a world-renowned expert on the disorder.

“I was impressed whenever Dr. Thornton called me and talked on the phone with me for close to an hour,” Perkins said. “I know he's a very busy man. So, we decided to go ahead and cancel our plan to go to Philadelphia.”

The Perkins worked together with a multidisciplinary team of obstetricians from Texas Health Harris Methodist Hospital and CHI experts from Cook Children’s to develop a game plan for Charlee’s birth.

"From the first moment I met with Mrs. Perkins and we talked about how we could help her prepare for the birth of her child with a rare disorder, I was impressed with her determination to ensure the best possible care for her baby from the moment of his birth," Dr. Thornton said. "Her sacrifice to leave her family and travel to Cook Children's so that she would be able to deliver her baby where our team was ready to treat him from birth was the best choice she could make."

But in the months that followed things went awry for Laurie. Preeclampsia and placenta abruption made for an early and dramatic delivery, throwing Charlee’s care team into action much sooner than originally anticipated. Charlee was born at 32 weeks gestation on July 7. As expected, his blood sugar was dangerously low. He was immediately transferred to Cook Children's and given medication to increase his blood sugar levels.

"By being prepared for a baby with severe hyperinsulinism we were able to have him stabilized within 30 minutes after birth," Dr. Thronton said. "This gave us the best possible ability to get a good long-term outcome for Charlee."

A Chance for Charlee

The Perkins had two treatment choices for Charlee. Either subject him to a lifetime of feeding tubes and continuous feeds to keep his blood sugar from dropping too low or have surgery to remove most of his pancreas. The latter would mean Charlee, like his big sister, would be a diabetic and dependent on insulin injections to regulate his blood sugar.

This time, the familiar made choosing the surgical option for their baby much easier. Charlee and big sister Ava have the exact same form of CHI. Ava’s pancreas was removed as an infant and, with the help of her family, she has been able to successfully manage the resulting diabetes. Even as an 11-year-old, she knows how to check her blood sugar, can read her glucose monitor and can change her cordless insulin pump. Nothing stops her from enjoying all of the activities in which kids her age take part. The Perkins knew they could instill the same knowledge, independence and confidence in Charlee as they have Ava.

Before they could do surgery, Charlee had to overcome the challenges of prematurity while in the NICU.

“Not only did he have CHI, but he had to beat all of the early preemie baby stuff to even be able to sustain surgery,” Perkins said. “He was born on July 7th at 32 weeks and was ready to rock and roll for major surgery on July 31.”

Meeting A Milestone

The Perkins family found Cook Children’s Hyperinsulinism Center in a milestone year, as 2020 marked the center’s 10th anniversary of serving children who come from all over the country to receive the very specialized care the center offers.

"The treatment of congenital hyperinsulinism is very complex," Dr. Thornton said. "It's really important that patients with rare diseases have access to multidisciplinary teams such as are at Cook Children's Hyperinsulinism Center where the approach and the experience of the team members caring for these patients results in better outcomes with shorter lengths of stay, getting the patient's home to their families as fast as possible."

Hayden Hood has been a Cook Children’s Hyperinsulinism Center patient since its inception. Doctors discovered Hood’s hyperinsulinism just weeks after his birth in 2000.

“Hayden was so sick when he was born that it took them a matter of days to figure out the problem,” said Davelyn Hood, M.D., Hayden’s mother and a family practice physician in San Antonio, Texas. “You hate to say that you’re grateful that your child is sick but, because he was so sick, they were able to diagnose him early. That’s why he’s had better outcomes than could have been.”

Most of Hayden’s pancreas was removed when he was two weeks old but the problem persisted. After struggling to manage his disease for the first 19 months of his life, the Hoods decided to travel from their home in South Texas to CHOP as it was the only HI center in the U.S. at that time. That’s where they met Dr.Thornton.

“Dr. Thornton helped us come up with a new treatment plan for Hayden, something that we could do to help stabilize his hyperinsulinism condition,” Dr. Hood said. “It was a real roller coaster in those days, and Dr. Thornton was a big part of helping get things on a more stable track for us.”

In what Hayden’s mom describes as a divine turn of events for their family, Dr. Thornton was recruited by Cook Children’s Medical Center in 2002 to join the medical staff as the medical director of endocrinology. The move meant the Hoods would no longer have to travel out-of-state for Hayden’s care.

Dr. Thornton spent eight years growing the Cook Children’s endocrinology program and, in 2010 set his sights on launching the nation’s second HI clinic at the medical center.

“Every child’s HI management is different. It’s a very personalized experience,” Hayden’s mom said. “I think that’s an important distinction. They don’t just have a one-size fits all treatment. At Cook Children’s they’re really able to tailor their care, and I think that’s why families feel heard and like they are getting care that works for them. That’s something extra special about the Cook Children’s center.”

Breaking Barriers

Like most rare disorders, there are few resources for information and support for families with HI, so the Perkins and Hoods led the way in building a few.

Laurie Perkins organized a support group in their parish called Sweet Heroes for children with diabetes so that Charlee and Ava can spend time with other kids who face a similar fate.

Dr. Hood parlayed her medical knowledge into an advocacy role as the president of the board for Congenital HI International, a nonprofit dedicated to improving the lives of those with HI. She is also a principal investigator for the HI global registry which collects data and feedback from HI patients across the globe in order to learn more about the HI experience. Dr. Thornton is active with this organization and endeavor as well.

Living with a rare disorder hasn’t stopped Hayden from pursuing his dreams. And, if his big sister is any indication, it won’t stop Charlee Perkins either.

“I always felt like a normal kid,” Hayden said. “I did every normal thing a kid can do and didn’t feel held back at all. I know I am one of the lucky ones with this disease. So I really do try to take everything as a blessing.”

Hayden went on to become a long snapper for the Texas Tech Red Raiders during his first year of college. Today, he has his sights set on creating a career path that allows him to nurture his love for hunting and ranching. He even started a small hunting guide business with a friend. Now a young adult, Hayden is able to manage his HI with diet, exercise and paying close attention to how his body feels.

"One of the best parts of being an endocrinologist and working in a single institution for a long time is getting to guide our patients from diagnosis all the way up to adulthood and seeing them become successful adults," Dr. Thornton said. "It's even more fun when the families follow you from one institution to another. The big advantage of seeing a child from diagnosis to adulthood is that you come to understand the lifelong impacts of a disease on a child and their family and this makes you a better doctor at the end of the day."

As for little Charlee, his days are full of kisses and cuddles from mom, dad and sister. He is meeting all of his milestones, loves to smile, is sitting up and will be crawling in no time.

To help raise awareness of this rare genetic cause of neurodevelopmental disease, M. Scott Perry, M.D., medical director of neurology and director of the Genetic Epilepsy Clinic at Cook Children’s, shares basic information about the disorder and exciting advancements towards treatment for this rare disease.

What do SCN2A-related disorders look like? 

Children with genetic variants in SCN2A can develop early onset epilepsy with various levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome that often occurs in multiple family members. These children can develop seizures as newborns or infants, but can develop normally with good seizure control.

Later, SCN2A was discovered as a cause of infantile spasms and other early onset severe epilepsies of childhood, the so-called early infantile epileptic encephalopathies. The gene has also been linked to Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. In addition, SCN2A variants are a major cause of intellectual disability, schizophrenia, and autism which may occur without associated epilepsy. A variety of other medical conditions may be present in people with SCN2A-related disorders, including sleep problems, cerebral palsy, and movement disorders to name a few.

What is the cause of SCN2A-related disorders? 

SCN2A is a gene which makes a sodium channel found primarily in the nerve cells that generate electricity. Two issues can occur with SCN2A. The first is a change in the gene which causes a gain of function – a change that allows too much sodium to enter the nerve cell and thus increases electricity – often presenting with epilepsy as a main symptom.

For others, SCN2A variants cause a loss of function – a change that decreases sodium entering the nerve cell and thus decreases electricity – more often presenting with autism and intellectual disabilities. Many mutations in SCN2A are de novo, meaning they occur spontaneously and were not inherited from the parents. This is often the case in more severe disease presentations. There are instances where SCN2A may be inherited from a parent and this is more commonly seen in benign presentations such as BFNIS.

How are SCN2A mutations diagnosed? 

Often, genetic testing can diagnose SCN2A mutations. The Behind The Seizure program provides free testing for children in the U.S. under the age of 8 years.

Magnetic resonance imaging (MRI) scans are often normal and electroencephalogram (EEG) findings may vary.

Is there a treatment for SCN2A-related disorders? 

While there is not yet a cure for SCN2A-related disorders, a significant amount of research is leading to exciting new therapies. Certain traditional sodium channel seizure drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in select patients (often gain of function), while in others, sodium channel drugs may aggravate seizures.

New drugs are being developed that specifically target the abnormal channel produced by SCN2A. These treatments may provide more precise control of the channel without disrupting the function of other sodium channels like many traditional sodium channel seizure drugs. This may result in better seizure control with less side effects.

Potentially most exciting is the development of genetic approaches to therapy, treatments that don’t just treat symptoms, but aim to correct the genetic abnormality. Antisense oligonucleotides (ASO) are small pieces of genetic material that can be given to help increase or decrease production of SCN2A. This approach has been used in other genetic conditions (spinal muscular atrophy and Dravet syndrome) with success and represents a promising therapy for SCN2A disorders as well. This is just one of several genetic approaches to therapy on the horizon.

Where can you find more information about SCN2A disorders?

For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org. The SCN2A Foundation serves as an excellent resource for information about SCN2A related disorders and helps connect a community of people living with these rare conditions. The site provides updates on SCN2A research as well.

Madisyn, 19, has suffered outbursts of pain that, at times, left her entertaining the idea that her life was too agonizing to continue.

“Here I am at the edge of 16 not being able to walk and my legs were on fire,” she said. “My legs were swelling up and I felt like my … bones were being crushed. My legs were turning purple, they were turning red. I had black spots all over me. I had white spots all over me, and no one knew what was going on.”

Read full story here.

Paul Thornton, M.D. is the medical director of Cook Children’s Hyperinsulinism Center, one of only two such centers in the U.S. and the only one in the southern portion of the country. He has dedicated his life to researching and treating congenital hyperinsulinsim (HI), and in turn has helped improve the quality of life for countless children.

Dr. Thornton’s work is so well respected he was recently named a Rare Disease Hero by Rare Disease Communications. The award recognizes five physicians each year for groundbreaking research and treatment in the rare disease community.

“Rare Disease Communications is proud to be honoring these real-life heroes,” said Chris Davis, president of Rare Disease Communications. “This is, indeed, a rare opportunity to applaud the silent victories that mean so much to patients and families.”

In addition to the Rare Disease Hero award, Dr. Thornton was also recently honored at the 2016 sugar sHIndig at the Fort Worth Science & History Museum where he was given the Be My Sugar Medical Excellence Award by Congenital Hyperinsulinsim International (CHI).

“It’s an honor to be recognized by the leaders in the congenital hyperinsulinism community,” said Dr. Thornton. “As we continue to treat children from across the country and the world, we’re excited to share information about our program and the excellent team providing quality, family-centered care.”