Saving Siena

The sweet smile on Siena Hale’s pretty face melts the hearts of those whom she encounters. Her inquisitive eyes quickly scan the visages that enter her orbit. She might extend her delicate hands to touch someone, but she cannot have a conversation with them.
Siena seems to be like millions of other 9-year-old girls, but she is one of fewer than 100 children in the world with a rare genetic disorder called ALG13-CDG, one type of a group of metabolic diseases known as congenital disorders of glycosylation, or CDG. ALG13-CDG is caused when a mutation arises spontaneously in someone’s ALG13 gene or is inherited. In Siena’s case it was spontaneous.
Nearly all children with ALG13-CDG experience neurological and developmental delays, muscle tone disorders, gastrointestinal problems, cortical visual impairment and seizures. Siena’s mother, Keszia Hale, says her daughter has the brain function of a 2-year-old.
There is no cure for ALG13-CDG, so parents of children like Siena are hoping to raise enough money to begin collaborating with the biotech company Perlara PBC on a drug repurposing project to find a potential treatment to improve the quality of life for their children.
Keszia and Bryce Hale are among the parents working to raise $150,000 through findingacureforalg13-cdg.org to complete the first three phases of the project, for things such as optimizing yeast avatars, drug repurposing screens and confirming findings.
“Our long-term fundraising goal is to continue to raise funds for future phases of the drug repurposing project (e.g., clinical trials) and to participate in any scientific research opportunities that arise for ALG13-CDG,” Keszia notes.
The Hale family lives on the Rainbow River in Dunnellon. Their home is a safe and fun haven for Siena and her sister Zenika, 7, who was not born with ALG13-CDG.
“Siena’s ‘big’ little sister is Zenika or ‘Zen,’ who loves, dance, gymnastics, baseball and acting,” Keszia notes. “The Rainbow River bonds us all together as we all love the water. I think Siena enjoys the water more than any of us.”
And, Keszia adds, “Every child like Siena needs someone who loves them exactly the way they are, and that is her daddy”.

“As you can imagine, Siena is my world. She is the sweetest child you have ever met and does not want for anything but just to be happy,” states Bryce Hale. “Finding a cure for this disease and giving her the ability to speak and communicate with us would be life changing. Everybody who meets her says she is the most wonderful happy child they’ve ever met. She is a positive influence on everyone she meets.”

The Journey

Keszia moved to Inverness in 2010 and commuted to work in Ocala at Collier, Jernigan & Goedert as their lead CPA auditor.
“My husband and I built our dream home in Dunnellon and moved in January 2015. Siena was born on March 18, 2015, at Monroe Regional Medical Center in Ocala,” she shares. “When Siena was 6 months old, a daycare worker saw her eyes roll while they were giving her a bottle and they called me in and said take your baby to the hospital right away. We went to the pediatrician, and they said, ‘Oh, that’s nothing, that’s something that they do. Within two days I was like, ‘Okay this is not nothing.’ She had lost hearing and vision. She couldn’t walk. She was like a ragdoll.”
She recalls that Siena was hospitalized and “they tested her for a million things under the sun and they couldn’t figure anything out.”
“The first step was to stop the chaotic brain waves with a nine-week steroid treatment of ACTH (adrenocorticotropic hormone), which cost over $32,000 per 5 milliter vial,” Keszia recalls. “Next, we attempted to gain seizure control. At barely 6 months old, Siena went through an array of tests—EEGs that burned her head, MRI’s, ultrasounds, EKG’s, spinal tap and an epilepsy panel.”
The steroid treatment worked for about two months. Keszia says doctors with UF Health tried anticonvulsants, which seemed to make things worse. At some point, “I said, I’m not disrespecting your opinion but I’m going get a second opinion and they said please do. We don’t know what’s going on.”
“We flew to Boston Children’s Hospital. They said to stay on the regimen and try to max it out. If that doesn’t work, try a ketogenic diet,” Keszia explains. “That was in September and by October I said this is not working.”
The Hales learned about Dr. Peggy Borum, research director of the precision ketogenic therapy program at UF Health.
“She’s amazing,” Keszia offers. “She said we must admit her to the hospital to get her on keto. We did that on December 4th by December 8th the seizures were gone.”
Adhering to the PKT diet required an extreme effort from Siena’s family, but it helped for nearly six years.
“Every one of her meals is measured to the 10th of a gram. It is 90% fat, 7% protein and 3% carbohydrates,” Keszia explains. “We have been in the program since December 2016 and feel as if it gave Siena a better life than was expected. She didn’t have another seizure until November 2023.”
“For more than a century, the medical community has used a starvation-mimicking diet known as the ketogenic diet to treat seizures. When antiseizure medications became more prevalent in the 20th century, the ketogenic diet lost favor because it was more labor intensive,” offers Borum, a professor of food science and human nutrition at the University of Florida in Gainesville.
“During the past 30 years,” she continues, “it has regained popularity with patients often seeing a greater reduction in seizures and fewer side effects compared to treatment with antiseizure medications. Nutrients are the chemicals we use to treat seizures as well as support the nutritional status of the patient. Our pediatric PKT clinic and adult PKT clinic both take the approach of creating a protocol that is precise and personalized for each patient.”
In addition to working with medical experts, Siena tried occupational, speech, physical, aqua and other kinds of therapies.
“We started in-home counseling with the Florida School of Deaf and Blind and in-home support from Early Steps (Florida’s system for those age birth to 36 months who have or are at-risk for developmental disabilities or delays) until Siena was 3,” Keszia notes. “Needless to say, between all the doctors’ visits, therapy and counseling, I quit my job at the CPA firm to provide the best care possible to Siena. And, finally, a whole exome sequence genetic test led to her diagnosis at 22 months old.”

The CDG CARE Community

The CDG CARE (Community Alliance and Resource Exchange) nonprofit 501(c)(3) was founded in 2014 by parents like the Hales.
“Our mission is to promote greater awareness and understanding of CDG, to provide information and support to families affected by CDG and to advocate for and fund scientific research to advance the diagnosis and treatment of CDG,” says Executive Director Andrea Miller, whose daughter Bianca, now 14, was diagnosed with PMM2-CDG as an infant.
“I witnessed firsthand the challenges of navigating a rare diagnosis and the critical gaps in care, resources, education and research. This inspired me to build an organization that empowers families, connects them with experts and drives advancements in treatment and quality of life for all children and young adults diagnosed with CDG,” she says.
Miller says ALG13-CDG research represents a crucial step forward for families like Siena’s because it addresses the unique challenges and medical complexities of this specific CDG type.
“Children with ALG13-CDG often face significant neurological and developmental challenges. Tragically, many lives have been lost to this medically complex disorder, making the pursuit of research not only essential but deeply personal for affected families,” she explains.
“While there is currently no cure for ALG13-CDG, each discovery from this research project brings us closer to tailored treatments and, ultimately, improved outcomes for the children diagnosed with this rare and devastating disease. For families, it offers hope—hope for better symptom management, a deeper understanding of their child’s condition and a clearer path to care. For families like Siena’s, this project embodies a collective effort to tackle the challenges of ALG13-CDG through science, innovation and community,” she shares. “Advancing this research not only impacts Siena but contributes to the broader CDG research landscape, offering insights that could benefit the entire CDG community.”

May 16 is CDG Awareness Day and offers a way for families to connect, along with an annual national conference. There are numerous social media components, including Facebook and YouTube presentations. Find Siena, for example, at fb.com/throughsienaseyes and youtube.com/@sienahale9274

Research Is Key

Siena has been part of a CDG study for five years and Keszia says that as part of the research, the “lead CDG doctor has taken cells and created a ‘mini brain’ of her—with a yeast avatar.” She offers that Perala PBC would be testing “more than 8,000 drugs or nutraceuticals on a yeast avatar that has her mutation.”
Perlara launched in 2014 as the first biotech public benefit corporation. Researchers and clinicians share expertise to guide cure and treatment paths.
“The research will use Perlara’s yeast-based screening platform to discover existing drugs that could be repurposed to treat ALG13-CDG. We begin by working with an ALG13 yeast patient avatar, an off-the-shelf yeast model engineered to mimic the disease. Yeast is an efficient and cost-effective research model for drug discovery, as it’s easy to grow in the lab and shares many genetic similarities with humans,” explains Kristin Kantautas, Ph.D., CDG Program Director, Perlara PBC.
“We start by measuring how the ALG13 yeast avatar grows compared to yeast with a healthy ALG13 gene. Since ALG13 is essential for yeast health, the patient avatar is expected to grow much more slowly. Next, we screen a library of 8,400 compounds—including FDA-approved drugs, drugs in clinical development, nutraceuticals and supplements—to identify those that improve the patient avatar’s growth,” Kantautas continues. “Promising candidates are then validated in follow-up studies in yeast and more advanced models, such as patient cells or ‘mini-brains.’ In cases where the top drug candidate is a readily available dietary supplement or nutraceutical, patient testing can often

begin immediately. Perlara’s approach accelerates the discovery of cost-effective treatments for rare genetic diseases like ALG13-CDG, offering hope for families impacted by these conditions.”
Kantautas says that as the world’s first biotech public benefit corporation dedicated to discovering treatments for rare diseases, Perlara has gained a lot of experience in drug repurposing.
“To date, we’ve discovered potential treatments for over 25 rare genetic diseases. Congenital disorders of glycosylation (CDG), including ALG13-CDG, are one of our core research areas,” Kantautas notes. “We currently have 13 active drug-repurposing programs focused on different types of CDG. So far, every screen has uncovered promising candidates, and in many cases, we’ve advanced to patient studies within a year. We’re optimistic that the ALG13-CDG program will follow a similar path to success.”
As for what ALG13 families might expect along the journey, Kantautas says each project at Perlara is led by a cure guide, which is a scientist or clinician with expertise in translating drug discoveries from the lab to the clinic.

“The first phase often moves quickly—sometimes in under three months—as we narrow down the list to the most promising options. The next steps depend on the type of candidate we discover and what’s needed to safely bring it into the clinic. We work closely with CDG researchers and clinicians across all our programs to move the research forward quickly,” she explains. “While the journey will include exciting moments and some waiting periods, our ultimate goal is to bring safe, effective treatments to patients as fast as possible.”
“The research with Perlara would help identify a treatment that would improve quality of life for ALG13-CDG kids,” Keszia offers. “This could mean Siena may be able to grow up, she may be able to make friends, she may be able to communicate her needs and express her feelings without so many tears. She may be able to avoid the pain and suffering that her peers experienced later in childhood. This research could be life changing to almost 100 families who don’t fit into any single group large enough for the FDA to notice they desperately need help to save their children from constant pain and suffering without any relief for their supporting families. This research is hope.”
As of December 27th, a little more than $41,000 has been raised out of a goal of $150,000 to help get the research started with Perala. Once the group obtains $90,000 in donations, Perala will begin its work.

To donate to help Siena’s family and others, go to secure.givelively.org/donate/cdg-care/finding-a-cure-for-alg13-cdg

To learn more, visit findingacureforalg13-cdg.org, cdgcare.org and perlara.com