CDG & Allies - Professionals and Patient Associations International Network (CDG & Allies- PPAIN)
Where families’ own needs and ideas are transformed into research projects.

Work Package 4 
Biology to guide CDG therapies

This Work Package (WP) is formed by several Working Groups (WGs)
Working Group (WG) CDG & Liver
Working Group Leader (WGL): Pf David Cassiman
(Head of the Hepatology Unit, Center for Metabolic Diseases and full Professor at KU Leuven, Belgium).

In CDG there is a multisystem involvement affecting various organs and structures, and one of them is the liver. The measurement of transaminases in the blood reflects the breakdown of cells from the liver. Fortunately, the liver has lots of reserve so slightly high transaminase levels need to be watched and assessed but are typically well tolerated. In most cases of CDG the transaminases may go rise and fall.

As the children grow older they remain normal but may sometimes elevate when the children become ill. There are, however, some affected individuals that have problems with elevated transaminases for longer times. In some types of CDG affected individuals may present with an enlarged liver, fibrosis and problems with the biliary pathway. The only CDG with an efficient treatment is MPI-CDG, is considered to be a hepato-intestinal disease. Although like most CDG, also MPI-CDG is probably underdiagnosed. The current project intends to increase awareness among the community of hepatologists, using a systematic literature review and educational materials as tools. 

Results obtained from this research project:
Any student, research groups, researchers, clinicians, patient organisations or other stakeholders who would like to become more involved within this project, are most welcome to get in touch to discuss possible future opportunities and collaborations. Fulfill the contact form available at the end of the page.

Pf David Cassiman

Biography:
Email: david.cassiman@kuleuven.be

​Dr. Cassiman received his Ph.D. in 2001 awarded by the Katholieke Universiteit (KU) Leuven. Prior to that he had completed his MD degree in 1996 at KU Leuven. Since the completion of his doctorate he has had a highly diversified career. From 2005 until last year, he was Associate Professor at the Faculty of Medicine at KU Leuven. Last year, he was assigned to the post of Full Professor at KU Leuven. Furthermore, since 2012 he also teaches at University of Hasselt. Moreover, at KU Leuven Dr Cassiman is head of the Hepatology Unit. Alongside his teaching career, Dr Cassiman continues to be a Medical Doctor at UZ Leuven, with focus on liver diseases and metabolic diseases. As far as his career as a Researcher is concerned, Dr Cassiman has been a half-time fundamental clinical researcher at Research Foundation Flanders (FWO) Vlaanderen for ten years now. The variety of his career posts can only be matched by the range of his research interests and projects. Currently, Dr Cassiman is the promotor of four research projects and co-promotor of one. His research interests include metabolic liver diseases (haemochromatosis), Wilson’s disease, rare inborn errors of metabolism, mitochondrial dysfunction, orphan diseases, orphan drugs and orphan drug regulations. Consequently, he has an extensive and remarkable list of publications in several relevant scientific magazines. He hopes his knowledge and work will ultimately make a difference in the lives of CDG patients. 

List of 6 publications in the field of CDG:
  1. Morel, T., Aymé, S., Cassiman, D., Morgan, M., Vandebroek, M. (2016). Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers. Orphanet Journal of Rare Diseases, accepted.
  2. Wolthuis, D., Janssen, M., Cassiman, D., Lefeber, D., Morava, E., Morava-Kozicz, E. (2014). Defining the phenotype and diagnostic considerations in adults with congenital disorders of N-linked glycosylation. Expert Review of Molecular Diagnostics, 14 (2), art.nr. 10.1586/14737159.2014.890052, 217-24.
  3. Picavet, E., Cassiman, D., Aertgeerts, B., Simoens, S. (2013). Development and validation of COMPASS: clinical evidence of orphan medicinal products – an assessment tool. Orphanet Journal of Rare Diseases, 8, art.nr. 157.
  4. Simoens, S., Picavet, E., Dooms, M., Cassiman, D., Morel, T. (2013). Cost-effectiveness assessment of orphan drugs: a scientific and political conundrum. Applied Health Economics and Health Policy, 11 (1), art.nr. 10.1007/s40258-012-0004-y, 1-3.
  5. Cassiman, D. (2011). Gene transfer for inborn errors of metabolism of the liver: the clinical perspective. Current Pharmaceutical Design, 17 (24), 2550-2557
  6. Laleman, W., Verbeke, L., Meersseman, P., Wauters, J., van Pelt, J., Cassiman, D., Wilmer, A., Verslype, C., Nevens, F. (2011). Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Review of Gastroenterology & Hepatology, 5 (4), 523-536.​
​
Well known professionals in the field of CDG are involved in this project:
  • Pf Dr Jaak Jaeken (Center for Metabolic Diseases, KU Leuven, Leuven, Belgium).
  • Dr Patrícia Janeiro (Departamento de Pediatria-Unidade de Doenças Metabólicas, Centro Hospitalar Lisboa Norte, Hospital de Sta. Maria, Lisboa, Portugal.

Vanessa Ferreira

About:
Email: sindromecdg@gmail.com
From her unique perspective of being a sister of a patient with a rare disease named Congenital Disorders of Glycosylation (CDG) and Cell Biologist, Vanessa founded the Portuguese CDG Association and other Rare Metabolic Disorders (APCDG-DMR).

Vanessa’s personal journey with her sister, combined with the community needs, have been the impetus to focus the APCDG activities.
​Vanessa received a bachelor’s degree in Biological Sciences from Badajoz University (Spain). She holds a PhD (Sc.D.) in Cell and Developmental Biology from the Center for Genomic Regulation, University of Pompeu Fabra, Biomedical Research Park in Barcelona (PRBB). In 2014, she completed her background with an International MBA from IAE de Paris, Sorbonne Graduate Business School.

Dr Patrícia Janeiro

Biography:
Dr Patrícia Janeiro  |  Metabolic Diseases Unit, Paediatric Department, CHLN, Hospital de Santa Maria, Lisbon, Portugal
Email: patricia.janeiro@gmail.com
Dr. Patrícia Janeiro graduated from Medical School at the Lisbon Medical University, Portugal in 2001. In 2002 and 2003 she performed the general medical internship at the Lisbon Civil Hospital. From 2005 to 2010 she trained as a paediatrician at the Fernando Fonseca´s Hospital, Amadora. In 2010 she became a consultant in paediatrics, working in the field of inborn errors of metabolism in the Metabolic Unit, Pediatric Department, Hospital de Santa Maria, CHLN, Lisbon.
She has published papers related to various items in paediatric matters such as neurocutaneous disorders, paediatric infectious diseases, nutritional management of newborns in ICU, and also in different metabolic diseases items such as disorders of cholesterol metabolism, trimethylaminuria, phenylketonuria, and fatty-acid β-oxidation defects.   

She has conducted lectures on various topics on metabolic inborn errors diseases such as phenylketonuria, metabolic encephalopathies, galactosemia, fatty acid β-oxidation defects, Gaucher disease, mucopolyssacharidosis, MSUD, organic acidurias, acute treatment and nutritional management of metabolic disorders, expanded newborn screening, mitochondrial disorders, and CDGs.

She has been involved in graduate and postgraduate training in metabolic diseases as well as master guidance of medical students.
She is member of the Board of the Portuguese Society of Metabolic Diseases since March 2014, and member of the Organizing and Scientific Committees of International Symposiums of SPDM.
​
She has collaborated as a co-organizer, with Dr. Ana Gaspar, in the course “Think Metabolic,Think CDG” Academy, in February 2016, an initiative from the CDG Portuguese Association, and participated in the translation of patient information flyers to the “Guia Metabolica”.

Pf Jaak Jaeken

Biography:
Professor Jaak Jaeken received his M.D. degree from the University of Leuven in 1967.  From 1967 to 1973 he trained in paediatrics at the same university. Subsequently he completed a research fellowship in metabolic diseases at the University of Zürich.

In 1975 he returned to Leuven. The contribution of Prof. Jaeken to medicine is exceptional, mainly in the field of metabolic disorders, due to the princeps-description of several metabolic diseases. In 1980, Prof. Jaeken was the first to describe  patients with a congenital disorder of glycosylation (CDG). He received his Ph.D. in 1985. In 1999 he received the degree of Doctor Honoris Causa from the University of Zürich, and in 2000 from the University of Havana. Since 2006, he is Emeritus Professor at the Faculty of Medicine. Prof. Jaeken is currently on the the Editorial Board of The Journal of Inherited Metabolic Disease (since 1994) and of Brain & Development (since 2004). He is a member of numerous societies and councils and he has received many prizes and honours. Prof. Jaeken’s publication list includes 517 papers, including 339 peer reviewed international publications, 2 books, 32 book chapters. He was guest editor of 2 special volumes on CDG. He hopes to continue working in the CDG field. He is an inspiration for the CDG community.

The list of the 6 publications with a major impact for CDG research: 
  1. JAEKEN J, VANDERSCHUEREN-LODEWEYCKX M, CASAER P, et al. Familial psychomotor retardation with markedly fluctuating serum proteins, FSH and GH levels, partial TBG-deficiency, increased serum arylsulfatase A and increased CSF protein: a new syndrome? Pediatr Res 1980; 14:179
  2. JAEKEN J, VAN EYCK HG, VAN DER HEUL C, CORBEEL L, EECKELS R, EGGERMONT E.  Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome.  Clin Chim Acta 1984;144:245-247
  3. JAEKEN J, SCHACHTER H, CARCHON H, DE COCK P, CODDEVILLE B, SPIK G.  Carbohydrate-deficient glycoprotein syndrome type II : a deficiency in Golgi-localized N-acetylglucosaminyltransferase II.  Arch Dis Child 1994; 71:123-127
  4. VAN SCHAFTINGEN E, JAEKEN J.  Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I.  FEBS Lett  1995;377:318-320
  5. JAEKEN J, Matthijs G, Saudubray J-M, et al.  Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation.  Am J Hum Genet 1998;62:1535-1539
  6. JAEKEN J, VLEUGELS W, REGAL L, et al. RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation (CDG). J Inherit Metab Dis 2009; 32:756-757​

Dr Peter Witters

Biography:
Dr Peter Witters  |  Centre for metabolic diseases, KU Leuven 
​email: peter.witters@uzleuven.be 
Dr. Peter Witters received his Ph.D. on the subject “Platelets, cholestatic liver disease and cystic fibrosis” from the KU Leuven in 2010. In 2013, Dr. Witters joined the Department of Paediatric Gastroenterology, Hepatology and Nutrition, at University hospitals Leuven and was appointed as a clinical faculty member at the Center for Metabolic diseases in 2014. In 2014, he was appointed as a Professor at the faculty of biomedical sciences, in KU Leuven. In 2016, Dr. Witters was awared a post-doctoral mandate of the Clinical Research Fund (KOF), University Hospitals Leuven. His interests are focused on hepatology, nutrition and gastroenterology. His work in the field of CDG is focused on uncovering liver disease in these patients. He aims to contribute to CDG lives by improving the understanding and, consequently, the treatment of liver disease. Dr. Witters’ work has been distinguished with a number of prizes and grants and repeatedly published in international peer-reviewed journals. He is a member of several national and international  medical societies.

List of 6 publications in the field of CDG:
  1. Morelle W, Potelle S, Witters P, Wong S, Climer L, Lupashin V, Matthijs G, Gadomski T, Jaeken J, Cassiman D, Morava E, Foulquier F. Galactose supplementation in TMEM165-CDG patients rescues the glycosylation defects.J Clin Endocrinol Metab. 2017 Article accecpted.
  2. Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D. Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis. 2017 Jan 20. [Epub ahead of print] 
  3. Witters, P. and Morava, E. 2016. Congenital Disorders of Glycosylation (CDG): Review. eLS. 1–6.
  4.  Morava E, Tiemes V, Thiel C, Seta N, de Lonlay P, de Klerk H, Mulder M, Rubio-Gozalbo E, Visser G, van Hasselt P, Horovitz DD, de Souza CF, Schwartz IV, Green A, Al-Owain M, Uziel G, Sigaudy S, Chabrol B, van Spronsen FJ, Steinert M, Komini E, Wurm D, Bevot A, Ayadi A, Huijben K, Dercksen M, Witters P, Jaeken J, Matthijs G, Lefeber DJ, Wevers RA. ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies.J Inherit Metab Dis. 2016 Sep;39(5):713-23.
  5. Witters P, Régal L, Waterham HR, De Meirleir L, Wanders RJ, Morava E. Normal ognitive outcome in a PEX6 deficient girl despite neonatal multisystem presentation.Am J Med Genet A. 2016 Jun;170(6):1642-6.
  6. Witters P, Hoylaerts M, Freson K, De Vos R, van Pelt J, Nevens F, Van Geet C, Cassiman D. ADP-degrading enzymes inhibit platelet activation in bile-duct ligated rats.J Thromb Haemost. 2010, Feb;8(2):360-8. 

The faces of CDG researchers involved in the project
​“Liver involvement in CDG”

Dorinda da Silva

Rita Francisco
Dorinda da Silva ​
Dr da Silva, received her Biochemistry degree in University of Algarve – Faro, Portugal. She defended her PhD thesis on “Study of redox and calcium transport systems microdomains in the plasma membrane of neurons”, in University of Extremadura – Badajoz, Spain. Her work is developed under the scope of the CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN).She integrated our working group since beginning February 2016. Dr Dorinda is highly motivated to make a difference in patients lives.
Rita Francisco
Rita Francisco has a Masters’ degree in Molecular Genetics by the University of Minho and among her main scientific interests are genetic disorders. In 2016, she was awarded the 3rd Liliana Scientific Scholarship. In March 2017, she won a PhD scholarship awarded by Fundação para as Ciências e Tecnologias (FCT) and she is now dedicating herself to unravelling the immunological aspects of CDG. Rita is highly driven and motivated to make a difference in the lives of adults and children living with Congenital Disorders of Glycosylation (CDG). Her work is developed under the scope of the CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN). In addition, she is our  CDG patient advocate manager and CDG International Patient Relations.

Open position!

Inés Summer Internship CDG for Undergraduate Students:
Currently the WP2 expressed interest in hosting a student to conduct summer research focused on diagnosis for CDG.
​This position is available under the scope of the “1st Inés Summer Internship CDG Program for Undergraduate Students”. 

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