CDG Archives - Sanford Burnham Prebys
Institute News

Sharing science and stories at Rare Disease Day Symposium

AuthorGreg Calhoun
Date

March 7, 2024

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.

Since 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.”

Rare Disease Day Welcome speakers, Malin Burnham, Hudson Freeze, David Brenner

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 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

Where science meets patients: Sanford Children’s Research Center hosts inaugural symposium

AuthorMiles Martin
Date

May 10, 2023

The event celebrated 16 years of progress at the Center and connected scientists with the people most impacted by their work.

The Sanford Children’s Health Research Center at Sanford Burnham Prebys recently hosted its first-ever Children’s Health Research Symposium, which brought scientists and families together to learn about the latest research tackling childhood diseases.

“We’re all here because we want to improve the health of children,” said President and CEO David A. Brenner, MD, during his opening comments. “But this event also shows the amazing amount of collaboration and collegiality across San Diego, because we have all types of people together from different backgrounds who want to develop therapies and cures for children affected by disease.”

The Sanford Children’s Health Research Center was established in 2008 with the help of a generous gift from Institute namesake T. Denny Sanford. Since then, the Center has been a world leader in children’s health research.

“T. Denny Sanford made an investment in children’s health 15 years ago, and I think that investment has paid off pretty well so far,” said Center director Hudson Freeze, PhD, in his introduction to the first scientific session. Freeze is among the world’s leading experts on congenital disorders of glycosylation (CDG), a rare group of genetic disorders that can cause serious, sometimes fatal, malfunctions of different organs and systems in the body.

“We’ve published over 600 scientific papers, and about half of those are translational studies, which means they’re helping turn scientific discoveries into real treatments for patients,” adds Freeze.

Professor Hudson Freeze with the Omler family

Professor Hudson Freeze with the Omler family

The day included presentations from researchers at Sanford Burnham Prebys, as well as from other research organizations studying childhood diseases. However, the highlight of the event was the afternoon reception, in which scientists had the opportunity to mingle and share a meal with families affected by rare childhood diseases.

Professor José Luis Millán (center) with the Fischer family (left) and the Britt family (right)

Professor José Luis Millán (center) with the Fischer family (left) and the Britt family (right)

Each researcher briefly introduced the family affected by the illness the scientist studies. This list included many longtime friends of the Institute, such as Damian Omler, who lives with a rare form of CDG; and Morgan Fischer, who was born with soft bone disease. Today, thanks to the help of a drug developed based on the research of Institute professor José Luis Millán, PhD, Morgan is a thriving teenager. This drug is also helping other children living with soft bone disease, including 10-year-old Aubrey Britt, who was in attendance with her family as well.

“Something so important that we keep as a tradition for scientific events at our Institute is to involve families that have been touched by the work of our faculty,” said Freeze. “They’re why we’re all here.”

The full list of talks included: 

Sanford Children’s Health Research Center

  • José Luis Millán, PhD “Developing therapeutics for soft bones and ectopic calcification disorders”
  • Duc Dong, PhD “From hope for few to drug for many—why rare is precious”
  • Evan Snyder, MD PhD “A clinical trial using human neural stem cells for neuroprotection in perinatal asphyxia, a major cause of cerebral palsy in kids”
  • Anne Bang, PhD “Drug screens of human-induced pluripotent stem cell (hiPSC) derived neuronal networks on multi-electrode arrays”
  • Pamela Itkin-Ansari, PhD “Proinsulin misfolding in diabetes”
  • Yu Yamaguchi, MD PhD “Multiple hereditary exostoses—from genetics to potential drug targets”
  • Hudson Freeze, PhD “Fucose therapy: Revising bedrock biochemistry”

Sanford Health

  • David Pearce, PhD “From rare diseases to type-1 diabetes: Research that impacts children at Sanford Health”

Frontiers in Congenital Disorders of Glycosylation Consortium

  • Eva Morava, MD, PhD “Clinical trials in Glyco-land”
  • Ethan Perlstein, PhD “Precision drug repurposing: Patient avatar to pioneer study to Phase 3 trial”

UC San Diego

  • Lars Bode, PhD “Human milk-based therapeutics and diagnostics to protect preterm babies from necrotizing enterocolitis”
  • Stephanie Cherqui, PhD “Hematopoietic stem cell gene therapy for cystinosis: Mechanism of action and clinical trial update”
Institute News

Rare Disease Day gathers scientists, doctors and families

AuthorMiles Martin
Date

March 3, 2022

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.

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

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

One at a time: How a Sanford Burnham Prebys professor changes patient lives

AuthorMiles Martin
Date

February 22, 2022

Having worked for decades to improve the lives of children with rare diseases, Hudson Freeze is still on the case.

Hudson Freeze, PhD is not your average researcher. His work focuses on congenital disorders of glycosylation, or CDG, a severe group of diseases that affect fewer than 2,000 children worldwide. Those conditions occur when sugar molecules on many of our proteins are absent or incomplete. That can lead to serious, often fatal, malfunctions in various organ systems throughout the body.

Although Freeze is not a clinician, he is deeply involved in identifying these rare CDG mutations, and providing families with answers to what is often a challenging diagnosis. Because CDG is a group of incurable diseases, families of children with CDG reach out to Freeze almost weekly, seeking help.

“If someone asks for help, I say, ‘Let me try,’” says Freeze. “Any glimmer of hope is a path worth pursuing, anything to make life easier for children with CDG.”

Freeze has been working on CDG for more than 25 years and has worked with more than 300 patients, and he has kept in touch with many of them over the years.

“Not a day goes by when I don’t think of them and their struggles—but mostly their smiles,” says Freeze. “It’s the reason we won’t give up on trying to understand them and maybe even finding treatments.”

Treating disease with sugar
Although CDG presents as permanent and irreversible mutations, Freeze’s research has been instrumental in discovering an approach to alleviate severe symptoms of CDG—such as seizures—in certain patients. The answer: sugar. Thanks to Freeze and others, there are about 30 patients worldwide who are now taking mannose, a simple sugar molecule, to help alleviate their CDG symptoms.

Today, the strategy of treating diseases with simple sugar molecules is being explored in other glycosylation disorders, as well as less-rare diseases such as multiple sclerosis, cancer and diabetes.

Hudson Freeze, PhD poses with Damian Omler, who has CDG.

Hudson Freeze, PhD poses with Damian Omler, who has CDG.

Rare Disease Day at Sanford Burnham Prebys
Freeze’s impact on the lives of families living with CDG extends well beyond the walls of his lab. Since 2010, he has organized an annual Rare Disease Day Symposium each February, where scientists, doctors and families gather from around the world to discuss the latest research and meet other families coping with rare diseases. Last year, the pandemic forced the Institute to press pause on the event, but this year, Rare Disease Day is back in San Diego and stronger than ever.

“It’s a chance for the global CDG community to come together, support one another and continue to put our heads together to find treatments,” says Freeze. “It’s always my favorite weekend of the year, and I’m thrilled that we’re able to do it again safely.”

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

Register Here

Institute News

Fighting rare diseases: Finding treatments and bringing hope to families

AuthorMonica May
Date

March 23, 2021

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

Families, physicians and scientists unite at Sanford Burnham Prebys’ 11th Annual Rare Disease Day Symposium

AuthorMonica May
Date

March 16, 2020

This year’s event centered on CDG, a rare genetic condition that affects around 1,500 people worldwide.

With more than 270 attendees and 30 world-renowned scientists and clinicians, Sanford Burnham Prebys’ 11th Annual Rare Disease Day Symposium was officially the largest in the event’s history. This year’s discussion centered on congenital disorders of glycosylation, or CDG, a rare genetic condition that affects around 1,500 people worldwide.

Malin Burnham, T. Denny Sanford and Debra Turner, honorary trustees of Sanford Burnham Prebys, opened the three-day meeting with moving remarks. A theme emerged: Medical advances are accelerated when key stakeholders work together—including scientists, physicians, people with CDG and their families, patient advocacy groups, granting agencies, industry and philanthropists.

“Our annual symposium aims to create an ecosystem in which key stakeholders can collaborate and communicate,” said Hudson Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys and symposium chair. “Together, we celebrate our successes, focus on challenges and discuss the future of CDG research.”

 

Presenters at the meeting described the power of the ecosystem. Since the first conference a decade ago where scientists reported on the basic biology of CDGs, today we have promising clinical trials for the most common CDG mutation. In addition, a historic nationwide effort to establish the natural history of CDGs launched this year—which addresses decades of unresolved questions and helps remove barriers to starting clinical trials.

First discovered in the 1990s, scientists now know that CDG is caused by mutations that disrupt the body’s normal process of attaching sugars to proteins. Children with CDG have varying degrees of speech and language difficulty, poor balance, motor control, vision problems, hearing impairments and seizures. 

Because CDG is rare, many patients bounce between doctors and clinics for years before they receive an accurate diagnosis. At the symposium, an innovative session called the “Doctor-is-in” session connects families with medical researchers and clinicians in small groups. For some medical researchers, the session is the first time they have met a person with CDG.

The conference was co-organized by Sanford Burnham Prebys and CDG CARE, a nonprofit organization founded by parents seeking information and support for CDG.

Institute News

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

AuthorMonica May
Date

October 3, 2019

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

Parents gain answers about their child’s mysterious condition, thanks to SBP scientists

AuthorMonica May
Date

December 11, 2018

For the parents of a six-year-old Hispanic boy and a seven-year-old Qatari girl, answers remained elusive. Both children had alarming symptoms, including developmental delays, uncontrollable seizures and “floppy baby syndrome” (hypotonia). But despite doctors’ best efforts, the origin of the disease remained unknown. 

Now, these two children are linked by rare mutations in a gene called FUK—providing their families and doctors a better understanding of the cause of their medical conditions. Using biochemical techniques to analyze the boy’s cells, Sanford Burnham Prebys Medical Research Institute (SBP) scientists determined that a malfunctioning enzyme called fucokinase is to blame—caused by a mutation in the FUK gene. Because cells from the girl weren’t available, computer modeling was used—and indicated this same mutation likely caused the disease. The study published in the American Journal of Human Genetics.

Like a molecular spark plug, the fucokinase enzyme ignites one step in a cellular communication cascade—which culminates in the linkage of a sugar, fucose, to another carbohydrate. This final fucose-carbohydrate product is important for immune system regulation, tissue development, cell adhesion (“stickiness” to the environment) and more. 

Based on these findings, the scientists now know the condition is a congenital disorder of glycosylation (CDG), an umbrella term for disorders caused by abnormal linking of sugars to cellular building blocks, including proteins, fats (lipids) and carbohydrates. Although more than 130 types of CDGs exist, the boy and girl are the only known living individuals who have this mutation. 

“Our hope is that by reporting this information, we will help doctors grant more answers to patients and their loved ones,” says Hudson Freeze, PhD, senior author of the paper and director and professor of the Human Genetics Program at SBP. “Based on our findings, genetic databases around the world will now note this mutation causes disease—a potentially life-changing shortcut in the quest for answers.” 

The researchers analyzed skin and immune cells that were collected from the boy. They observed reductions in the amount of the fucokinase enzyme—as much as 80 percent in skin cells and more than half in immune cells, compared to a control protein. Consistent with these findings, downstream products typically created by fucokinase weren’t incorporated into the final fucose-carbohydrate product—indicating the enzyme was not working.

Because cells from the girl were not available, the scientists used computer modeling to predict the impact of her FUK gene mutation. This approach indicated the mutation occurs at an important site on the enzyme that would likely cause disease.

“We know that dampening down the activity of the FUK gene is linked to metastatic cancer—a deadly event that occurs when tumors gain the ability to travel throughout the body,” says Freeze. “In addition to providing long-awaited answers to these families, these findings could help us understand how certain cancers spread throughout the body, including liver, colorectal and skin cancers (melanoma).” 

Both children were identified through the National Institutes of Health’s Undiagnosed Diseases Network, which is designed to accelerate discovery and innovation in the way patients with previously undiagnosed diseases are diagnosed and treated. 

Additional study authors include: Jill Rosenfeld, Lisa Emrick, MD, Lindsay Burrage, MD, PhD, Brendan Lee, MD, PhD, William Craigen, MD, PhD, Baylor College of Medicine; Mahim Jain, MD, PhD, Johns Hopkins School of Medicine; David Bearden, MD, University of Rochester School of Medicine; and Brett Graham, MD, PhD, Baylor College of Medicine and Indiana University School of Medicine. The study’s DOI is https://doi.org/10.1016/j.ajhg.2018.10.021

Research reported in this story was supported by National Institutes of Health (NIH) grants R01DK099551, U01HG007709, and K08DK106453; Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (U54 HD083092), Diana & Gabriel Wisdom and the Rocket Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. 

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.