About This Project
Our research team recently discovered a new genetic disease that affects sugar metabolism and leads to severe low blood sugar levels in children. We don't yet know how frequently this disease occurs, and more important, all the ways in which it affects children. Excitingly, we have found a treatment for the disease. Using blood samples from enrolled patients, we can answer these questions and start treating these children.Ask the Scientists
Join The DiscussionWhat is the context of this research?
Hypoglycemia, or low blood sugar level, is the most common metabolic condition in young children. Without understanding the reason for a child’s low blood sugar level, treatment becomes unreliable and subsequent low blood sugar levels may be life-threatening. Accordingly, this project is investigating the following key questions:
- What is the frequency of this newly discovered yet treatable genetic disease that causes severe low blood sugar in young children?
- Can we diagnose the disease in time to avoid the associated long-term brain damage?
- What are the clinical symptoms of this disease?
What is the significance of this project?
We will evaluate the occurrence of a newly identified treatable disorder in young children. Children born with this disease, called congenital glycosylation defect (CDG), have difficulties to assemble sugar chains from sugar residues and cannot attach the sugar chains to their body proteins.
Last year we discovered a treatable form of this disease. Patients with the disease suffer from low blood sugar levels in the first few years of life. If the disease is undetected, children may develop seizures and brain damage. Fortunately, if this condition is diagnosed early, these symptoms are fully treatable. Sadly, we are currently unaware of how many patients have this new disease.
We want to find and treat children born with this disease to improve our understanding of the sugar chain assembly defect and the associated symptoms.
A simple screening method, transferrin isoelectric focusing, will be used to identify children with this new condition. Using a single drop of blood or blood plasma, this method analyzes the number of sugar chains in the patients’ blood and determines the amount of milk sugar residues missing from the patients’ blood proteins. The results of this study will provide important insights on a new disease for pediatricians, primary care physicians, laboratory experts and scientists .
What are the goals of the project?
Beginning in 2014, we hope to recruit and then enroll 250 patients for this project. Using 1 mL of blood or plasma collected from each participant, we will screen all patients for suspected low blood sugar level and then further explore their blood for a possible sugar chain-building defect. In addition to screening for liver function problems, we intend to collect information about the clinical symptoms, age of presentation, and laboratory abnormalities characteristic of this newly discovered disease.
Budget
Awarded funding will be applied to direct laboratory costs (purchasing necessary reagents for blood analysis and blood analysis procedures - $5500), data collection costs (blood sample shipping and storage- $3000) and patient confidentiality and privacy costs (safe data management - $500). The apparatus for the sample screening is already available and not included in this budget.
Meet the Team
Team Bio
The goal of the current investigation is to establish screening for congenita disorders of glycosylation in Louisiana and establish screening and dietary intervention in PGM1 deficiency, a disorder recently discovered by our research team as a cause of hypoglycemia. Eva Morava has a history of leading successful collaborations on translational research projects in the past, both with American and European research groups, demonstrated by prestigeous multicenter publications. She is higly motivated in translational research bringing clinicians and geneticists, scientists and students involved in the biochemical genetics field together. The current project on a novel metabolic disease discovered by her group and collaborators has high potential for developing new scentific and diagnostic methods, bridging clinitians to basic scientists, building scientific collaborations and training young staff and graduate students in high level research.Eva Morava
Ever since I remember I wanted to be a pediatrician and I was always intrigued by genetics. Finding the diagnosis in a rare genetic condition and offering counseling empowers families. It is not only about learning about their child's condition but also the first step towards treatment. Discovering new disorders is a great success but also a huge responsibility; we are obliged to find the patients with the novel condition and initiate therapy as soon as possible.
Press and Media
The Advocate on Morava's research and CrowdfundingAdditional Information
Recent publications on congenital disorders of glycosylation1. Wolthuis DF, van Asbeck EV, Kozicz T, Morava E. Abnormal fat distribution in PMM2-CDG. Mol Genet Metab. 2013 Nov;110(3):411-3.
2. van de Loo KF, van Dongen L, ..., Lefeber DJ, Morava E, Verhaak CM. Socio-emotional Problems in Children with CDG. JIMD Rep. 2013;11:139-48.
3. Linssen M, Mohamed M, Wevers RA, Lefeber DJ, Morava E. Thrombotic complications in patients with PMM2-CDG. Mol Genet Metab. 2013 May;109(1):107-11.
4. Verstegen R, Theodore M, van de Klerk H, Morava E. Lymphatic edema in congenital disorders of glycosylation. JIMD Rep. 2012;4:113-6.
5. Funke S, Gardeitchik T, Kouwenberg D, Mohamed M, .., Lefeber DJ, Morava E. Perinatal and early infantile symptoms in congenital disorders of glycosylation. Am J Med Genet A. 2013 Mar;161A:578-84.
6. Barone R, Aiello C, Race V, Morava E, Foulquier F, Riemersma M, Passarelli C, Concolino D, Carella M, Santorelli F, Vleugels W, Mercuri E, Garozzo D, Sturiale L, Messina S, Jaeken J, Fiumara A, Wevers RA, Bertini E, Matthijs G, Lefeber DJ. DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy. Ann Neurol. 2012 Oct;72(4):550-8.
7. Morava E, Vodopiutz J, Lefeber DJ, ..., Lehle L, Wevers RA. Defining the phenotype in congenital disorder of glycosylation due to ALG1 mutations. Pediatrics. 2012 Oct;130(4):e1034-9.
8. Timal S, Hoischen A, Lehle L, ..., Wevers RA, Morava E, Veltman J, Lefeber DJ. Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing. Hum Mol Genet. 2012 Oct 1;21(19):4151-61.
9. Mohamed M, Theodore M, ..., Kouwenberg D, Lefeber DJ, Wevers RA, Morava E. Thyroid function in PMM2-CDG: diagnostic approach and proposed management. Mol Genet Metab. 2012 Apr;105(4):681-3.
10. Kapusta L, Zucker N, Frenckel G, ..., Wevers RA, Lorber A, Morava E. From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG). Heart Fail Rev. 2013 Mar;18(2):187-96.
11. Binkhorst M, Wortmann SB, Funke S, Kozicz T, Wevers RA, Morava E. Glycosylation defects underlying fetal alcohol spectrum disorder: a novel pathogenetic model. "When the wine goes in, strange things come out" - S.T. Coleridge, The Piccolomini. J Inherit Metab Dis. 2012 May;35(3):399-405.
12. Theodore M, Morava E. Congenital disorders of glycosylation: sweet news. Curr Opin Pediatr. 2011 Dec;23(6):581-7.
13. Mohamed M, Cantagrel V, Al-Gazali L, Wevers RA, Lefeber DJ, Morava E. Normal glycosylation screening does not rule out SRD5A3-CDG. Eur J Hum Genet. 2011 Oct;19(10):1019.
14. Lefeber DJ, Morava E, Jaeken J. How to find and diagnose a CDG due to defective N glycosylation. J Inherit Metab Dis. 2011 Aug;34(4):849-52.
15. Morava E, Lefeber D. CDG - an update. J Inherit Metab Dis. 2011 Aug;34(4):847-8.
16. Achouitar S, Mohamed M, ..., Elson J, Morava E. Nijmegen paediatric CDG rating scale: a novel tool to assess disease progression. J Inherit Metab Dis. 2011 Aug;34:923-7.
15. Mohamed M, Guillard M, .., Gardeitchik T, Kouwenberg D, Lim BC, Zeevaert R, Wevers RA, Lefeber DJ, Morava E. Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern. Biochim Biophys Acta. 2011 Jun;1812(6):691-8
Morava lab short overview
Hayward genetics at Tulane University
Scientific output by Researchgate Portugese CDG association
Project Backers
- 4Backers
- 3%Funded
- $250Total Donations
- $62.50Average Donation