CDG Archives - Sanford Burnham Prebys

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Institute News

Sharing science and stories at Rare Disease Day Symposium

AuthorGreg Calhoun
Date

March 7, 2024

Rare Disease Day 2024 group photo

The Sanford Burnham Prebys Rare Disease Day Symposium brought patients, families, physicians, scientists, industry experts and advocates together with a focus on congenital disorders of glycosylation.

Sanford Burnham Prebys, in partnership with CDG CARE and the Sanford Children’s Health Research Center, hosted a Rare Disease Day Symposium in San Diego from March 1-3, 2024. The goal of the event was to share the latest scientific developments from researchers studying congenital disorders of glycosylation (CDG), and to foster new perspectives, ideas and collaborations to accelerate the creation and implementation of better therapies and treatment plans for those living with CDG.

CDG is an umbrella term for more than 190 disorders caused by mutations that impair glycosylation; the complex process by which cells build long sugar chains that attach to proteins called glycoproteins. CDG affects fewer than 2,000 children worldwide. When glycosylation is impaired, the sugar molecules on many of the body’s proteins are absent or incomplete, leading to serious, often fatal, malfunctions in various organ systems throughout the body.

Rare Disease Day Welcome speakers, Malin Burnham, Hudson Freeze, David BrennerSince 2010, Hudson Freeze, PhD, the William W. Ruch Distinguished Endowed Chair, professor and director of the Human Genetics Program, and director of the Sanford Children’s Health Research Center at Sanford Burnham Prebys, has organized an annual Rare Disease Symposium, where scientists, doctors and families gather from around the world to discuss the latest research and meet other families coping with rare diseases.

“At Sanford Burnham Prebys, we’re committed to rare disease research,” says David Brenner, MD, president, CEO and Donald Bren Chief Executive Chair at Sanford Burnham Prebys, during his welcoming remarks. “We believe we can make a unique contribution to society with this work, and in so doing make the world a better place.”

Brenner noted that Rare Research Day marked a time for academic medical centers across the US to celebrate the synergy between patients, families, physicians and scientists that is needed to advance research on all rare diseases, including CDG.

This was reflected throughout the symposium’s schedule and in the tenor of individual presentations. Patients and families were invited to give talks throughout the weekend to discuss the perspective of living with CDG or caring for a family member with CDG. The physicians and scientists who spoke consistently credited the patients and families for all they do to help raise funds and participate in research, including clinical trials that can add more appointments to already challenging calendars and routines.

The family reception on Friday, March 1, concluded the first day of the symposium with a more informal opportunity for patients, families, doctors and researchers to connect and socialize.

“This is the largest meeting we’ve ever had,” notes Freeze. “This gathering is an important part of nurturing the CDG research ecosystem by bringing experts together while also knitting us closer together with the people who really matter – the families.”

The symposium’s many sessions over three days included:

  • Friday, March 1
    • Scientific meeting
      • Introduction and welcome from Sanford Burnham Prebys president and CEO, David Brenner; Malin Burnham and Debra Turner, philanthropists and honorary trustees; and Congressional Representative Scott Peters from California’s 52nd Congressional District
      • Discussion of perspectives, challenges and triumphs led by parents, patients and advocates
      • Sessions on new therapies in development, the potential use of biotin as a treatment for many CDG patients, neurological disease, and gene therapy approaches, among others 
    • Poster session
    • Family reception
  • Saturday, March 2
    • Scientific meeting
      • Keynote address on “Accelerating Treatment and Cures for Rare Diseases” from Joni Rutter, PhD, director of the National Center for Advancing Translational Sciences in the National Institutes of Health
      • Additional conversation about the experiences of parents and advocates
      • Sessions on clinical trial updates; especially strong were drug repurposing efforts leading to new and unexpected potential treatments
    • Doctor-is-in-session
      • Brought together medical researchers, clinicians, advocates, patients and their families for an afternoon of hands-on collaboration in small groups
      • Prior “Doctor-is-in-session” events have led to profound experiences and unlikely partnerships
    • Evening reception
  • Sunday, March 3
    • CDG CARE Scientific and Family Conference
      • CDG clinical care and management sessions included neurophysiology and epilepsy, growth charts and hormonal abnormalities, puberty and bone health
      • CDG research sessions included genetics 101, CDG updates, organoids as disease models and clinical trials as a partnership between physicians and patients, among others
      • CDG resource exchange sessions included educational planning and advocacy, speech and technology, therapy interventions, special needs planning and behavioral health and family planning
Institute News

Hudson Freeze joins experts to discuss testing to help CAD-affected children

AuthorSusan Gammon
Date

November 10, 2023

Hudson Freeze, PhD at his desk in his office

Hudson Freeze joined an international panel of genetics experts on CAD deficiency: Beyond the genetics—a podcast offered by the Journal of Inherited Metabolic Disease.

The researchers shared how clinical and functional genomics tests can accelerate the diagnosis of CAD-deficient patients and enable their timely treatment with uridine, a nutritional supplement that has dramatically improved the lives of other children with the condition.

“The effect of uridine for some children with CAD deficiency is nothing short of amazing. These kids go from bedridden to interacting with people and moving around,” says Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys. 

CAD deficiency is a congenital disorder of glycosylation (CDG), an umbrella term for more than 170 disorders caused by mutations that impair glycosylation; the complex process by which cells build long sugar chains that attach to proteins called glycoproteins.

These tests allow us to identify CAD genetic variants, and to help affected children get the best treatment possible,” adds Freeze.
 

Institute News

Rare Disease Day gathers scientists, doctors and families

AuthorMiles Martin
Date

March 3, 2022

Large group of people gathered in front of marina at Sunset

The 2022 Rare Disease Day Symposium took place last weekend at the Dana On Mission Bay Resort in San Diego. The event, sponsored by Sanford Burnham Prebys and CDG CARE, brought together researchers, clinicians and families from around the world to discuss new medical breakthroughs and meet other families living with rare diseases.

Rare Disease Day is celebrated on the last day of February to raise awareness for rare diseases, defined by the United States government as those that affect fewer than 20,000 people. Although there are more than 7,000 individual types of rare diseases that affect more than 30 million people in the United States, this year’s conference gathered more than 200 people focused on CDG, an extremely rare group of genetic disorders that affect children. 

CDG, which stands for congenital disorders of glycosylation, occurs when sugar molecules on many of our proteins are absent or incomplete. CDG causes serious, often fatal, malfunctions in various organ systems throughout the body.

“This is a chance for the global CDG community to come together, support one another and continue to try to find treatments,” says Hudson Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys. “It’s always my favorite weekend of the year, and I’m thrilled that we’re able to do it again safely.” Freeze’s primary research focus is CDG, and he has personally worked with more than 300 patients. 

Exchanging knowledge
The three-day symposium opened Friday morning with introductory comments from three important figures and philanthropists in Sanford Burnham Prebys’ history: T. Denny Sanford, Malin Burnham and Debra Turner. Congressman Scott Peterson also spoke on the importance of funding medical discoveries. 

“Our job is to make a positive difference. We do that best when we all work together,” said Sanford in his video introduction. “Congratulations on all your work. You make me very proud.”

This year, 19 scientists and clinicians in total spoke on the latest research in modeling, treating and understanding CDG. The full program of presentations can be found here.

Connecting families
Although Rare Disease Day is an important opportunity to share the latest scientific research, one of the highlights of the event doesn’t involve science at all. To provide space for families to take a break from the presentations and socialize, staff and volunteers transformed the Bayside Conference Room of the Dana resort into a child care and respite area packed full of toys and games.

In addition to giving families space to play, Rare Disease Day hosted several group activities for families, including a magic show on Saturday and a surprise visit on Sunday morning from Disney’s Anna and Olaf.

​Longtime friend of the institute Damian Omler, a thirteen-year-old who is the only person living with his rare genetic mutation, had a great time dancing along to “Let it Go” and playing catch with his father, Donnie.

And while the joy in the respite conference room was palpable, there was something else, less tangible, in the air as well: hope.

“Meetings like this bring us hope and help us raise awareness for CDG,” says Donnie. “That gives us a sense of purpose each and every time we attend the conference. And we won’t stop, even 20 years from now.” 

Omler family​
Damian Omler and his family, parents Donnie and Gracie and brother DJ, had a great time at Rare Disease Day the year (image credit: CDG CARE)
Institute News

Rare disease in the time of COVID: Damian Omler’s story

AuthorMiles Martin
Date

February 25, 2022

Omler family at Damian's 5th grade graduation

How a one-of-a-kind kid and his family stay connected during the pandemic

Thirteen-year-old Damian Omler is the only person in the world with his rare genetic mutation, which presents him and his parents (Donnie and Gracie) and 11-year-old brother, DJ, with major challenges every day. Damian’s condition—a congenital disorder of glycosylation, or CDG—causes him to have seizures, and requires him to have help with routine tasks such as using the restroom and dressing. And, he must use a wheelchair for mobility.

Despite these obstacles, Damian lives a rich, fulfilling life. But protecting his health during the COVID-19 pandemic threw a major wrench into the Omlers’ routine.

“In the early days of the pandemic, we didn’t know what kind of effect COVID would have on Damian, so we had to take a lot of precautions, including not seeing a lot of family and friends, which was very isolating,” says Donnie. 

“Damian is also very sociable—we call him the hot potato because he just goes from person to person, so the pandemic was hard for him in that way as well,” adds Gracie. “We were so glad when we were finally able to get our family vaccinated so we could be more a part of the community.”

Staying at home had its ups and downs for the Omlers
Although most of us can relate to the isolation of the pandemic, there are unique challenges that come with being a family living with a rare disease during this time. 

“Appointments were so much more difficult for Damian over Zoom,” says Gracie. “I had to help him through his physical therapy, and I was nervous that I might be doing it wrong or even hurting him.”

Despite these complications to Damian’s care, there were some unexpected silver linings to spending more time at home.

“Damian does choir and dance for his electives at school,” says Gracie. “I love that with remote learning I was able to interact with him and the class and learn the dances with him.”

“She definitely got a lot of accolades from the teachers for being one of the parents who participates,” adds Donnie, jovially. 

Returning to Sanford Burnham Prebys’ Rare Disease Day
The Omlers are longtime friends of Sanford Burnham Prebys. They first visited the Institute in 2012, when Damian was 5. Before then, they’d been struggling to find a diagnosis for their son, who’d been missing developmental milestones since he was born. 

With the help of Institute professor Hudson Freeze, PhD, who has dedicated his career to CDG research, doctors were finally able to diagnose Damian’s specific case in 2015. 

“After the diagnosis, we sat and smiled for a long time,” says Donnie. “Just knowing was such a relief.”

Since 2016, the Omlers have also been regular participants in the Institute’s Rare Disease Symposiums, which help patients, researchers and clinicians from around the world connect in order to support one another and learn about the latest advances in rare disease research.

The most recent Rare Disease Day the Omlers attended was in 2020, just before the pandemic took hold. And although the event didn’t take place last year, this year it’s back stronger than ever. And the Omlers can’t wait to be back too.

“Meetings like this bring us hope and help us raise awareness for CDG,” says Donnie. “That gives us a sense of purpose each and every time we go. And we won’t stop, even 20 years from now.” 

The 2022 Rare Disease Day Symposium & CDG/NGLY1 Family Conference will take place February 25–27 at the Dana Hotel on Mission Bay in San Diego. Scientific sessions will be held on the 25th and 26th, and the Family Conference will take place on the 27th.

And if you see a young man acting like a social “hot potato” on the 27th, that’s Damian. He’ll probably say hi to you.

Institute News

Fighting rare diseases: Finding treatments and bringing hope to families

AuthorMonica May
Date

March 23, 2021

Hudson Freeze, PhD and José Luis Millán, PhD

The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition that is incurable.

The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition that is incurable.

Often, their own doctors have never heard of their disease, let alone know how to treat it.

But there is someplace they can turn to for help. The Human Genetics Program at Sanford Burnham Prebys provides insights into the genes and environmental factors that play a role in the development of childhood diseases. Their work often leads to better ways to diagnose, treat, and sometimes, even cure children.

On March 18, 2021, two patients whose lives were saved by discoveries made by Hudson Freeze, PhD, and José Luis Millán, PhD, joined the scientists for a conversation about what this work means to them and how their lives have been impacted. Watch the full discussion below.

Institute News

Sanford Burnham Prebys scientist joins historic effort to help children with rare disease

AuthorMonica May
Date

October 3, 2019

Hudson Freeze, PhD

Hudson Freeze, PhD, professor of Human Genetics at Sanford Burnham Prebys, has joined a historic effort that establishes—for the first time—a nationwide network of 10 regional academic centers, Sanford Burnham Prebys researchers and patient advocacy groups to address decades of unresolved questions surrounding congenital disorders of glycosylation, or CDG, a rare disease that affects children. The consortium is funded by a $5 million, five-year grant from the National Institutes of Health (NIH). 

“We are extremely pleased that the NIH is investing in an initiative that will improve the lives of people affected by CDG,” says Freeze, who leads efforts to develop and validate disease biomarkers that will aid in diagnoses, and measuring treatment benefits during clinical trials. “Although globally the number of people living with CDG is relatively small, the impact on the lives of these individuals and their families can be profound. We look forward to working with the patients, families, physicians, scientists and other stakeholders focused on this important study.”

CDG is caused by genetic mutations that disrupt how the body’s sugar chains attach to proteins. First described in the 1990s, today scientists have discovered more than 140 types of mutations that lead to CDG. Symptoms are wide-ranging, but can include developmental delays, movement problems and impaired organ function. Some children may benefit from a sugar-based therapy; however, developing treatments for those who need alternative treatment options has been hindered by a lack of natural history data—tracking the course of the condition over time—comprehensive patient registry, and reliable methods to establish the CDG type.

Working together, the consortium will overcome these hurdles by: 

  • Defining the natural history of CDG through a patient study, validating patient-reported outcomes and sharing CDG knowledge 
  • Developing and validating new biochemical diagnostic techniques and therapeutic biomarkers to use in clinical trials 
  • Evaluating whether dietary treatments restore glycosylation to improve clinical symptoms and quality of life

Freeze will lead the efforts to develop and validate biomarkers for CDG, working alongside the Children’s Hospital of Philadelphia and the Mayo Clinic. The principal investigator of the CDG Consortium Project is Eva Morava, MD, PhD, professor of Medical Genetics at the Mayo Clinic. The patient advocacy groups involved are CDG CARE and NGLY1.org. 

Sanford Burnham Prebys and CDG Care will host the 2020 Rare Disease Day Symposium and CDG Family Conference from February 28 to March 1 in San Diego, which welcomes researchers, clinicians, children with CDG and their families, and additional CDG community members. Register to attend. 
 

Institute News

Meeting the “man who saved my son’s life”

AuthorMonica May
Date

November 15, 2018

Saraa and Baraa Ghoniem and Hudzon Freeze-CDG

“I’ve got really cool stuff in my body,” 6-year-old Baraa Ismail proclaimed to Hudson Freeze, PhD, professor in the Human Genetics program at Sanford Burnham Prebys Medical Discovery Institute (SBP).

And, indeed, he does. 

Baraa and his mother, Sara, didn’t know it at the time, but he was born with a rare change in his DNA that interfered with his body’s ability to attach a sugar to proteins—altering the course of his life. 

From birth, Baraa struggled with eating. He dealt with upset stomachs and lethargy, which is unusual for a young child. Sara searched high and low for an answer, but doctor visit after doctor visit, year after year, Baraa remained undiagnosed. 

After four years of uncertainty, Sara connected with Dr. Tawhida Yassin Abdel Ghaffar. She suspected a rare condition called congenital disorders of glycosylation (CDG) and ordered a test. Her instincts were correct—Baraa had one form of CDG. More than 130 types of the condition exist.  

In addition to working with her doctor, Sara was introduced to a new online community of parents and individuals with CDG. It was through a private Facebook group that she connected with another parent whose child has CDG. He told her, “You have to talk to Hudson Freeze at SBP.”

For more than three decades, Freeze and his team have studied CDG with the ultimate goal of developing a treatment. When Freeze heard from Sara, he recommended that she talk to her doctor about giving Baraa mannose, a nutritional supplement. 

Years ago Freeze helped discover that mannose can treat one specific form of CDG—incredibly reversing symptoms as quickly as days sometimes (note: Freeze is not a medical doctor). But it only works if a person has one kind of mutation; treatments are still limited for the 129 other types of CDG that exist. Freeze reasoned that even if he didn’t have Baraa’s genetic sequence in hand, if the boy had that mutation, the mannose would work. 

Incredibly, it did. Within a month, Baraa’s energy was back. And today, Baraa is a Flash-loving, book-devouring little boy who loves to run and sing. 

Baraa was doing so well that Sara even decided to take a vacation for the first time in years. She and Baraa traveled from their home in Egypt to visit her brother in Irvine, California—which happened to be a short drive from SBP. Sara reached out to Freeze, whom she calls “the man who saved my son’s life,” to see if a visit was possible. Freeze was delighted to meet with her and Baraa and give them a tour of his lab. 

“Really, my role was very small in this story,” says Freeze. “But what this illustrates is the importance information has for these families. A simple piece of information changed someone’s life. We’d love to grow so we can eventually become a true hub of information for these families—and help even more people like Sara and Baraa.”  

Institute News

“A Grand Canyon Aria” benefits SBP research

AuthorHelen Hwang
Date

June 4, 2018

CDG

A father’s love never dies, even when his child has succumbed to a fatal childhood disease. Alex Syed paid tribute to his daughter, Aria, by running a marathon through the majestic Grand Canyon in May 2018. Ten years ago, Aria passed away after suffering from congenital disorders of glycosylation, known as CDG—a disease that affects the way proteins and sugar molecules interact in the body.

In honor of his daughter, Syed raised more than $4,300 from 71 donors to fund important research in the laboratory of Hudson Freeze, PhD, professor and director of the Human Genetics Program at Sanford Burnham Prebys Medical Discovery Institute (SBP). Freeze is one of the world’s leading experts on CDG.

“Funding is always in short supply, so the donations that Alex raised in the name of Aria will bring us closer to finding a cure for other kids suffering from this devastating disease,” says Freeze. “Aria’s cells are in our lab to support experiments that will help build a database for possible therapies,” he adds.

To prepare for the run, which Syed dubbed “A Grand Canyon Aria,” he rose in the middle of the night to begin his 26-mile run from the South Rim via Bright Angel to North Rim, taking him over the mighty Colorado River.

Running through the Grand Canyon to raise money for Dr. Freeze’s research was Syed’s idea. He knows that rare genetic diseases do not receive a lot of funding from large pharma companies. “The almost-angelic work that Dr. Hud Freeze and his team are performing at SBP is truly unique,” says Syed.

To donate, go to sbpdiscovery.org/CDG.

Watch the video of Alex Syed’s run through the Grand Canyon in memory of Ari:

Watch the video from Dr. Hudson Freeze’s lab:

Institute News

Diagnosing a rare disease in children

AuthorSusan Gammon
Date

February 6, 2018

Rare disease

Children born with the rare genetic disorder known as CDG often live for years before they receive a diagnosis.  CDG—which stands for congenital disorders of glycosylation—can cause serious, sometimes fatal, malfunction of different organs and systems in the body, including the nervous system, muscles and intestines. Children with CDG have varying degrees of speech and language difficulty, poor balance, motor control, vision problems, hearing impairments and seizures.

CDGs are difficult to diagnose partly because there are only about 1,800 known cases worldwide. But through global networking and the unwavering determination of researchers and clinicians, new patients are being discovered every year, providing important information to parents to help them better understand what they are dealing with.

Hudson Freeze, PhD, director and professor of the Human Genetics Program at SBP, is a one of the scientific leaders helping diagnose new cases of CDG. Freeze and his colleague, Bobby Ng, recently led an international team charged with diagnosing three unrelated individuals thought to have a new type of CDG—but not confirmed. The work, published in the American Journal of Human Genetics, confirmed that the three had a specific kind of CDG never seen before, adding to the more than 125 existing types of CDGs.

“All CDG disorders are caused by mutations that impair glycosylation—the complex process by which cells build long sugar chains that are attached to proteins called glycoproteins,” explains Freeze. “These sugar chains are crucial for cellular growth, communication and essential cell functions.

“There are many genes involved in proper glycosylation,” says Freeze. “When two parents happen to carry a mutation on the same gene, they end up with a one-in-four chance of passing both mutated copies on their child, and that causes the disorder.”

Increasingly, babies and children with unexplained health problems such as developmental delays and organ dysfunction undergo whole-exome sequencing, a technique that sequences the part of the genome that encodes proteins.

“Exome sequencing is used to find mutations in genes, but sometimes we don’t know if the mutations found actually translate to a genetic condition like CDG,” says Ng.

“Our lab steps in when a suspected mutation is found in one of the many enzymes involved in glycosylation,” says Ng. “We perform biochemical tests to confirm that the mutation impairs the glycosylation process, helping families narrow in on a CDG diagnosis.”

“The three patients in the current study are the only confirmed cases of the FUT8-CDG type in the world,” says Freeze. “These very rare diagnoses are only made possible when physicians, researchers and parents reach out across continents to families who’ve had nothing but questions.”

For the past 8 years, SBP has organized an annual symposium in San Diego where scientists, doctors, and families gather to discuss the latest in science and medicine, and meet other families coping with rare diseases.

For more information on the 2018 SBP Rare Disease Day Symposium and CDG Family Conference, click here.

Institute News

Study triples the number of known cases of a rare disease

Authorjmoore
Date

March 10, 2016

Header image

A recent paper from the laboratory of Hudson Freeze, PhD, characterizes 39 previously unreported cases of a specific type of congenital disorder of glycosylation (CDG). CDGs, the focus of research in Freeze’s lab in SBP’s Sanford Children’s Health Research Center, are rare inherited disorders. CDG symptoms, which can include developmental delay, movement problems, and impaired function of multiple organs, differ depending on the underlying mutation. Continue reading “Study triples the number of known cases of a rare disease”