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.
-end-
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 http://www.ClinicforSpecialChildren.org

Clinic for Special Children

Related Children Articles:

Do children inherently want to help others?
A new special section of the journal Child Development includes a collection of ten empirical articles and one theoretical article focusing on the predictors, outcomes, and mechanisms related to children's motivations for prosocial actions, such as helping and sharing.
Children need conventional CPR; black and Hispanic children more likely to get Hands-Only
While compressions-only or Hands-Only CPR is as good as conventional CPR for adults, children benefit more from the conventional approach that includes rescue breaths.
Cohen Children's Medical Center study: Children on autism spectrum more likely to wander, disappear
A new study by researchers at Cohen Children's Medical Center of New York suggests that more than one-quarter million school-age children with autism spectrum disorder or other developmental disorders wander away from adult supervision each year.
The importance of children at play
Research highlights positive strengths in developmental learning for Latino children in low-income households based on their interactive play skills.
Racial disparities in pain children of children with appendicitis in EDs
Black children were less likely to receive any pain medication for moderate pain and less likely to receive opioids for severe pain than white children in a study of racial disparities in the pain management of children with appendicitis in emergency departments, according to an article published online by JAMA Pediatrics.
More Children News and Children Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...