Nav: Home

Researchers publish largest description of ST3GAL5 (GM3 Synthase) deficiency

February 05, 2019

STRASBURG, PA- Researchers have combined the largest description of ST3GAL5 (GM3 synthase) deficiency using detailed natural history data from 104 individuals of Amish ancestry born between 1986 and 2017 with a definite or probable diagnosis of ST3GAL5 deficiency. The study examined objective measures of biochemistry, auditory function, brain development, and caregiver burden. GM3 synthase is encoded by ST3GAL5, and is essential for synthesis of the most biologically relevant gangliosides in mammals.

The study, led by clinicians, represents a collaborative effort by the Plain Community Health Consortium (PCHC). PCHC is a network of non-profit clinics across five states that diagnose and treat rare genetic disorders in children from the Anabaptist communities. In addition to the Clinic for Special Children, the PCHC clinics include Center for Special Children in La Farge, WI, The Community Health Clinic in Topeka, IN, Nemours duPont Pediatrics in Dover, DE and New Leaf Center in Eaton, OH. The study appears in this month's issue of Molecular Genetics and Metabolism.

The report includes a detailed clinical characterization of the ST3GAL5 deficiency phenotype, which includes somatic growth failure, progressive microcephaly, irritability, blindness, deafness, involuntary movements, intractable seizures, and psychomotor arrest. Researchers used available medical records and structured interviews as the basis for data collection within Amish populations across five states. In addition to records and interviews, electroencephalograms (EEGs), audiology tests, irritability, and Parent Stress indexes, genealogical records, glycosphingolipid analysis, and newborn hearing screens were used to fully characterize the natural course of this rare and devastating disease.

This comprehensive study provides a rich baseline against which to judge the effectiveness of new disease-modifying therapies. ST3GAL5 deficiency is often diagnosed within hours of life, before the onset of neurological damage, which has motivated efforts to develop pre-symptomatic therapies. Liver transplantation might provide some benefit to children with the ST3GAL5 deficiency, but is contingent on the passage of GM3 through the blood-brain barrier. ST3GAL5 gene replacement holds promise but faces two significant obstacles. Current adeno-associated viral (AAV) gene vectors deliver to only a minority of central neurons. Strategies for better AAV design or repeat dosing may circumvent this problem. Mice have been useful in understanding human ST3GAL5 deficiency but pose challenges for pre-clinical treatment studies. Pigs more closely model human neurodevelopment and may prove more suitable for studying ganglioside-deficient brain diseases. While the study's initial findings suggest that these therapies might be successful for ST3GAL5 deficiency, researchers note that in-depth studies are warranted to determine the best potential treatments for ST3GAL5 deficiency.
The research was conducted by a team including the study's lead author Lauren E. Bowser, from the Clinic for Special Children, Strasburg, PA; senior author Kevin A. Strauss from the Clinic for Special Children, Strasburg, PA; Millie Young, Karlla W. Brigatti, Vincent J. Carson, Erik G. Puffenberger, Donna L. Robinson, Christine Hendrickson, and Adam D. Heaps from the Clinic for Special Children, Strasburg, PA, Olivia K. Wenger from the New Leaf Center, Mount Eaton, OH, Zineb Ammous and Teresa Moser from the Community Health Clinic, Topeka, IN, James Deline from the Center for Special Children, La Farge, WI, Kazuhiro Aoki and Michael Tiemeyer from Complex Carbohydrate Research Center, University of Georgia, Athens, GA, Thierry Morlet from Auditory Physiology and Psychoacoustics Research Laboratory, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, Ethan M. Scott from Department of Pediatrics, Akron Children's Hospital, Akron, OH, Jonathan Salvin from the Division of Pediatric Ophthalmology, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, and Steven Gottlieb of the Division of Pediatric Neurology, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE.

This study was funded in part by LaJolla Pharmaceuticals, Inc. (LaJolla, CA). No author received direct compensation or holds a commercial interest in the company.

About the Clinic for Special Children

The Clinic for Special Children (CSC) is a non-profit organization located in Strasburg, PA, which provides primary pediatric care and advanced laboratory services to those who suffer from genetic or other complex medical disorders. Founded in 1989, the organization provides services to over 1,0750 active patients and is recognized as a world-leader in translational and precision medicine. The organization is primarily supported through community fundraising events and donations. For more information, please visit

Clinic for Special Children

Related Children Articles:

Preterm children have similar temperament to children who were institutionally deprived
A child's temperament is affected by the early stages of their life.
Only-children more likely to be obese than children with siblings
Families with multiple children tend to make more healthy eating decisions than families with a single child.
Children living in countryside outperform children living in metropolitan area in motor skills
Residential density is related to children's motor skills, engagement in outdoor play and organised sports. that Finnish children living in the countryside spent more time outdoors and had better motor skills than their age peers in the metropolitan area.
Hispanic and black children more likely to miss school due to eczema than white children
In a study that highlights racial disparities in the everyday impact of eczema, new research shows Hispanic and black children are more likely than white children to miss school due to the chronic skin disease.
Children, their parents, and health professionals often underestimate children's higher weight status
More than half of parents underestimated their children's classification as overweight or obese -- children themselves and health professionals also share this misperception, according to new research being presented at this year's European Congress on Obesity (ECO) in Glasgow, UK (April 28-May 1).
Children with autism are in 'in-tune' with mom's feelings like other children
New research addresses limitations of prior autism spectrum disorder (ASD) studies on facial emotion recognition by using five distinct facial emotions in unfamiliar and familiar (mom) faces to test the influence of familiarity in children with and without ASD.
First Nations children and youth experiencing more pain than non-First Nations children
First Nations children and youth are experiencing more pain than non-First Nations children, but do not access specialist or mental health services at the same rate as their non-First Nations peers, found new research published in CMAJ (Canadian Medical Association Journal).
Grandparents: Raising their children's children, they get the job done
Millions of children are being raised solely by their grandparents, with numbers continuing to climb as the opioid crisis and other factors disrupt families.
How do you assess pain in children who can't express themselves? New research identifies priorities in identifying pain in nonverbal children with medical complexity
Pain is a frequent problem for children with complex medical conditions -- but many of them are unable to communicate their pain verbally.
Under age 13, suicide rates are roughly double for black children vs. white children
A new study published in JAMA Pediatrics shows that racial disparities in suicide rates are age-related.
More Children News and Children Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at